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Oral Delivery Oct 06 18/1/07 20:19 Page 2
Company profile
Published by ONdrugDelivery Ltd, Cedar Cottage,
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BN6 9BU, United Kingdom. Registered in England:
No 05314696.
The views and opinions expressed in this issue are those of the authors.
Due care has been used in producing this publication, but the publisher
makes no claim that it is free of error. Nor does the publisher accept
liability for the consequences of any decision or action taken
(or not taken) as a result of any information contained in this publication.
INTRODUCTION
Despite phenomenal advances in the inhalable, The message that pharmaceutical companies The increasing
injectable, transdermal, nasal and other routes usually send to would-be oral technology number of oral fixed-
of administration, the unavoidable truth is that partners is: only those with technologies that are dose combinations
oral drug delivery remains well ahead of the highly differentiated, fulfil needs that are near reaching the market and their growing acceptance
pack as the preferred delivery route. There are impossible to meet elsewhere, and are proven in by the medical and regulatory communities is
of course many applications and large markets the market place, need apply. highlighted by InnerCap Technologies. The
for non-oral products and the technologies that company’s multiphase, compartmentalised capsule
deliver them. However, if it is a viable option, Nevertheless, although the environment is technology, NovaCaps, both meets the existing
oral drug delivery will be chosen in all but the tough, success is possible. Indeed, a thriving oral needs for developing oral combinations, and
most exceptional circumstances. Moreover, if drug delivery sector does exist and it is expands the potential application of combinations
the oral route is not immediately viable, populated by innovative companies involved in into areas not previously considered possible.
pharmaceutical companies will often invest fruitful collaborations with pharma and biotech
resources in making it viable, rather than partners. I will divide these successful oral drug Finally, we are pleased to include here a piece
plumping for an alternative delivery method. delivery technologies into two broad categories: from Emisphere Technologies. Its eligen drug
carrier technology for delivering fragile
In a presentation last year, John Lynch, Chief 1. technologies which represent the crème de la macromolecules via the oral route has the
Operating Officer of Merrion Pharmaceuticals crème among many available systems addressing potential to bring the Holy Grail, oral drug
said that the oral drugs market generated US$26 a common delivery need (such as modified- delivery, within the reach of biologics companies
billion sales in 2004 and would experience 16% release or orally disintegrating tablets) and others for whom oral delivery has
growth up to 2008. He added that orally traditionally been viewed as out of the question.
delivered products accounted for 84% of the sales 2. highly specialised technologies meeting a With a remarkable claim such as this, the
of the top 50 selling drugs worldwide. niche demand or a need with a high company has met with scepticism and even
technological barrier to entry (for example, oral derision over the years. Having made significant
Oral products go from strength to strength, delivery of fragile macromolecules, or precision progress and generated robust data despite its
but the oral drug delivery sector is by no means release at specific locations within the GI tract) critics, here it presents encouraging evidence that
an easy one to succeed in. In fact it has to some eligen does indeed fulfil its promise.
extent become a victim of this popular delivery In this issue we are delighted to present
route’s success. Firstly, drug discovery efforts articles from six of the leading names in oral drug The primary purpose of this publication is to
are directed at generating compounds that are delivery. It is of course up to the reader to decide provide a platform from which companies can
readily orally deliverable and have the right into which, if either, of the two categories above describe their oral drug delivery systems and
pharmacokinetic/pharmacodynamic profile the technologies described might fall. outline their merits using scientific data and study
without the need for any specialised delivery results. However, during the process of choosing a
technology. Secondly, when an oral drug Various aspects of oral drug delivery are drug delivery partner it is important not to
delivery technology is needed, it is common for covered including: oral controlled-release; orally underestimate the significance of “soft factors” –
pharma companies to develop them in-house. disintegrating tablets (ODTs); fixed-dose essentially the factors such as company culture,
It’s worth the effort because the technology is combination capsules; oral macromolecular business practices and individual employees’
likely to be useful to them in the future since the delivery; and the move to a specialty pharma personalities, which decide whether a good day-to-
majority of products in the pipeline are business model. day working relationship between two
administered orally. Thirdly, the potentially organisations will be possible. This is especially
large rewards of developing a successful oral Three of the articles in this issue are contributed important when considering a shortlist of similar
delivery system have meant that the market is by companies discussing their ODT systems. Side technologies fulfilling similar functions.
now awash with hundreds, if not thousands, of by side, these provide an insightful comparison of
undifferentiated oral drug delivery companies competing technologies, and taken together the In addition to enabling those readers seeking
with equally undifferentiated technologies. papers provide a detailed overview of the latest partnerships for oral drug delivery systems to
developments, current issues and trends within this learn about the technologies described in terms
For pharma companies requiring a third rapidly growing sub-sector of oral drug delivery. of science, specifications and compatibility with
party technology to deliver their compounds, it their own needs, it is my intention that this
is difficult to find the right partner. For the The contribution from Penwest publication should also allow the reader, through
delivery companies hoping to enter, although Pharmaceuticals discusses the recent approval and the written word of the authors, to get to know
the sheer size of the oral delivery technology launch of Opana ER and the first definitive step in the companies themselves a little in terms of
market could to some extent improve the its strategy to leverage its oral drug delivery their business strategy, manner and style.
chances and potential degree of success, things expertise in the transformation from a technology
are significantly more difficult than they might provider to a specialty pharmaceutical company Guy Furness
initially seem. focused on neurology. Publisher
ORAL FAST DISSOLVE TECHNOLOGY IS OFTEN EMPLOYED WITH SUCCESS AS PART OF PRODUCT
LIFECYCLE MANAGEMENT STRATEGIES, AND IS POPULAR IN THE OTC AND PRESCRIPTION ONLY
MARKETS. HERE, DR IAN MUIR, VICE-PRESIDENT OF OPERATIONS AT CARDINAL HEALTH, EUROPE,
GIVES AN OVERVIEW OF THE CURRENT TECHNOLOGY LANDSCAPE, DISCUSSES STRENGTHS
AND LIMITATIONS, AND LOOKS AT HOW THE MARKET WILL DEVELOP IN THE FUTURE.
The drug delivery sector of fast dissolve products The lyophilised systems have been by far the
has grown rapidly from sales in 2002 of about $850 most successful among them in terms of sales
million to 2005 were estimated sales were around value, sales volume and number of worldwide
$1.4 billion (IMS Data). Despite this success there product approvals. The technology around these
is no agreed regulatory definition of what consti- systems involves taking a suspension or solu-
tutes a true fast dissolve product. It is generally tion of drug with other structural excipients and,
accepted that products fall into this field if they dis- through the use of a mould or blister pack, form-
solve in the mouth in less than 30 seconds, which ing tablet-shaped units. The units or tablets are
is what distinguishes them from traditional effer- then frozen and lyophilised in the pack or
vescent, chewable or immediate release tablets. mould. The resulting units have a very high
There are some class characteristics, which all porosity (see figure 1), which allows rapid water
fast dissolve products have in common (see table or saliva penetration and very rapid disintegra- Dr Ian Muir
1). In fact the market has really been defined by tion. Figure 2 shows an orodispersible tablet Vice-President of Operations at
Cardinal Health, Europe
the success of the various proprietary fast dissolve (ODT) produced using Cardinal Health’s Zydis
delivery systems and their ability to meet the needs technology, disintegrating over three seconds.
North American Contact:
of the patient, formulators and marketing groups. Dose-handling capability for these systems Stacey R. Vaughan
The use of drug delivery technology in the differs depending on whether the active ingredi- Cardinal Health
product management lifecycle is well known to all ents are soluble or insoluble drugs, with the Director Business Development
Zydis North America
in the pharmaceutical sector. Key to the success of dose capability being slightly lower for the for- 14 Schoolhouse Rd.
a drug delivery-based application is that there is a mer than for some tablet based systems. The Somerset, NJ 08873
T: 610-667-2511
clear unmet need or benefit to the use of the chosen units are capable of incorporating a range of F: 610-667-2950
system. A technology selection process is most suc- taste-masked materials and have more rapid dis- Mobile: 610-716-6611
cessful when considering the market, patient and integration than tablet-based systems (table 3). E: stacey.vaughan@cardinal.com
clinical requirements and increasingly the reim- Compressed tablet-based systems are produced
bursement environment for the product. Bringing using standard tablet technology by direct com- Rest of World Contact:
Michele Stokes
these four factors together significantly enhances pression of excipients. Depending on the method Regional Account Manager
the chances of market acceptance. Some examples of manufacture, the tablet technologies have dif- Cardinal Health, International
of considerations in each area are listed in table 2. ferent levels of hardness and friability. This results Sedge Close
Headway, Great Oakley
in varying disintegration performance (see table 3) Corby
FAST DISSOLVE TECHNOLOGIES and packaging needs, which can range from stan- Northamptonshire NN18 8HS
dard HDPE bottles or blisters through to more spe-
For ease of description, fast-dissolve tech- cialist pack designs for product protection – CIMA Mobile: 07919 044666
nologies can be divided into three broad groups: Labs’, PackSolv, for example. E: michele.stokes@cardinal.com
lyophilised systems, compressed tablet-based The speed of disintegration for fast-dissolve http://www.cardinal.com/pts/
systems, and thin film strips. tablets compared with a standard tablet is
cal companies, for in-house development of line Cost-effective manufacture Palatable product Bioequivalence Price versus
convenience for OTC
extension and generic fast-dissolve dosage forms
Stable device or packaging Cost effectiveness
- -
ORAL FILMS Proven regulatory & market
track record. - - -
Although oral film systems, the third class, Table 2: Key considerations in technology platform evaluation
have been in existence for a number of years,
they have recently become the new area of inter- entered the ethical prescription market.
est in fast-dissolve pharmaceutical drug delivery. In contrast the market for thin film strips is
This is largely as a result of the success of the mainly in the consumer vitamins, minerals and
consumer breath freshener products such as supplements (VMS) and OTC areas. Active
Listerine PocketPaks in the US consumer market. ingredients which appear to be suitable are vita-
Such systems use a variety of hydrophilic mins, supplements such as melatonin and
polymers to produce a 50-200 mm film of mate- CoQ10, and some OTC ingredients. An example
rial. This film can reportedly incorporate soluble, of the type of developments in this area are the Figure 1: Magnified cross section of a
insoluble or taste-masked drug substances. The deals between Bioenvelop and NutriCorp, who lyophilised ODT, showing the highly
film is manufactured as a large sheet and then cut have approval for a range of products in Canada porous structure
into individual dosage units for packaging in a including benzocaine, caffeine and menthol. To with novelty and ease of use. On a clinical level
range of pharmaceutically acceptable formats. give another example, Leiner Health Products this can translate into better compliance.
There remain a number of technical limita- have an exclusive deal to sell MonoSol film strips For some drugs capable of being absorbed via
tions with the use of film strips. The volume of for OTC products, the first of which is reported as the pre-gastric route, the use of a fast-dissolve sys-
the dosage unit is clearly proportional to the size a melatonin supplement. tem can result in the drug being absorbed more
of the dose, which means these extremely thin quickly and more reproducibly, compared with a
dosage forms are best suited to lower-dose prod- RATE OF DISINTEGRATION standard tablet. In these specific cases the speed of
ucts. As an example of this, Labtec claim that the dispersion, and therefore the relative amounts of
RapidFilm technology can accommodate doses One question, often asked, is whether the rel- drug retained in the mouth or the proportion of the
of up to 30 mg. This clearly limits the range of ative speed of disintegration is important in the dosage form swallowed before dispersing, could
compatible drug products. The other technical selection between fast-dissolve products. At a make a difference to the pharmacokinetic profile.
challenge with these dosage forms is achieving general level there are various reports in the sci- Drug molecules which are likely to be suit-
dose uniformity and unit dose packaging, which entific literature and from consumer preference able for delivery via this pre-gastric route are
is an area for differentiation in the technology studies, which show patient preference for fast generally soluble in saliva and have a high parti-
providers such as LTS and Cardinal’s DelStrip. dissolve over a standard tablet if they are given tion coefficient (log P>1) – characteristics often
The much-heralded advent of major branded the choice. This preference is usually linked associated with CNS active compounds. A good
products in this area still seems some way off.
This may be partly due to the technical difficul-
ties of taste masking and dose loading, but also
the fact that there appears to be fewer commer-
cial barriers to entry into this field.
In 2001 and 2002 it was reported that many
significant therapeutic products would launch
using this technology over the next two or three
years. Whilst there has been a five-fold increase 1 seconds 2 seconds 3 seconds
worldwide in the number of thin film strips
since 2002, very few if any such products have Figure 2: Rapid disintegration of a lyophilised Zydis tablet in minimal volume of water
Product Technology Diameter Start End example where this route of administration has
(mm) (seconds) (seconds) been used to commercial and clinical advantage
is the Zydis based selegiline product, Zelepar.
Alavert 10mg CIMA 10.0 22.7 32.8 The ODT version provides equivalent therapeutic
Benadryl Fast Melt - 11.2 10.9 15.7 plasma levels to the 10 mg standard oral tablet
with doses of only 1.25 mg and a resulting reduc-
Claritin Reditabs Zydis 11.1 0 3.8
tion in the metabolite associated side effects.
Excedrin Quicktabs - 17.5 11.8 25.8 Currently, products developed and manufac-
tured using Cardinal Health’s Zydis, CIMA Lab’s
Maxalt MLT Zydis 11.0 0 1.8
Orasolve and Janssen’s in-house Quicksolv tech-
NuLev CIMA 14.0 7.9 13.9 nologies account for more than 75% of US sales
Remeron Soltab Quicksolv 9.7 22.3 56.6 of fast-dissolve products (see table 4).
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Penwest Pharmaceuticals is implementing a strategy to make the change from being a drug
delivery technology provider to a specialty pharma company. This article outlines how
Penwest (Danbury, Connecticut, US) is currently implementing this change. By drawing on
its reputation for technical excellence in oral controlled release, and choosing its product
development targets intelligently, Penwest is moving forward to attain its goal of becoming a
specialty pharma company, marketing its own portfolio of neurology products.
Penwest’s business has been built on developing is indicated for chronic moderate-to-severe pain
sophisticated yet simple oral controlled-release in patients requiring continuous, around-the-
systems. In the late 1990s, Mylan clock opioid treatment for an extended period of
Pharmaceutcial’s Nifedipine XL was the first time. Opana ER is well protected from competi-
generic controlled release nifedipine to be tion by several barriers to entry. The FDA has
approved, and utilised the proprietary TIMERx® granted three-year exclusivity, and the product
technology. The product demonstrated scientific benefits from a strong, multilayered IP estate
excellence by meeting the challenge of mimick- strategy. Other barriers to generic entry include:
ing the release profile of Alza/Pfizer’s limited availability of the active compound; the
Procardia® XL. Its release was followed by sev- substantial technical challenge of avoiding (par-
tial or complete) disinte- Dr Anand Baichwal
Chief Scientific Officer and Senior
PENWEST IS ACTIVELY LOOKING TO gration of the formula- Vice-President of Licensing
tion when coming into
BROADEN ITS EARLY STAGE DRUG contact with alcohol,
something that could
DEVELOPMENT PIPELINE BY INVESTIGATING lead to dose dumping
IN-LICENSING NCES IN SELECTED AREAS (which TIMERx over-
comes but which is an
OF NEUROLOGICAL THERAPEUTICS issue with some other
technologies); and com-
eral other proprietary oral delivery systems – pliance with FDA risk-management strategies.
including Geminex® and SyncroDose™ - and a Beyond the US launch, Endo and Penwest are
Thomas Sciascia, MD
gastro-retentive technology (see figure 1 for also evaluating the international opportunity for Chief Medical Officer
more details of these technologies). Opana ER. Opana ER’s forecasted revenue
Penwest’s transformation started with the stream is an important component in funding
Penwest Pharmaceuticals
2003 sale of its excipients business to the Penwest’s growth over the years ahead.
39 Old Ridgebury Road
German firm Josef Rettenmaier Holding GMBH The product is the result of a long-standing Suite #11
and Co. KG, which demonstrated Penwest’s collaboration with Endo Pharmaceuticals, Danbury
commitment to pursuing drug development. This which already marketed an i.v. version and was CT 06810
United States
was followed by Penwest’s partner Endo looking for an experienced drug delivery com-
Pharmaceuticals submitting an NDA to the US pany that could provide a controlled-release
FDA for Opana® ER, the oral controlled-release technology for an oral formulation. T: +1 203 796 3700
formulation of the opioid analgesic oxomor- Development costs were shared equally P: +1 203 794 1393
E: bizdev@penwest.com
phone, which utilises the TIMERx technology. (50/50). Endo took responsibility for clinical tri-
Opana® ER was approved on June 22, 2006 als and the regulatory process, manufacturing www.penwest.com
and is available in 5, 10, 20 and 40 mg tablets. It and marketing. Penwest brought the technology
Figure 1: Opana® ER. FDA approved June 22 2006, August 14 2006, launched by Endo’s sales force August 14, 2006
(TIMERx), product formulation and IP, and tration. In contrast, Opana ER appears to be a at disorders of the nervous system. Opana ER
receives a royalty on profits. true twice-daily formulation. will be a significant asset as Penwest continues
Opana ER enters a market for long-acting In a 12-week, randomised, double-blind, to develop its product portfolio.
strong opioid analgesics valued at US$3.2 bil- placebo-controlled study, 250 opioid-experienced
lion (2005), and the timing of its launch may be patients with chronic low back pain, entered the CNS FOCUSED PORTFOLIO
fortuitous for several reasons. First, physician study with a pain score of 70 out of a possible 100,
hesitancy over long-acting opioids is waning, indicating moderate to severe pain, despite receiv- Two factors have driven the company’s speciali-
and a recent WHO guideline supports the use of ing treatment with another opioid. Patient ratings sation in the therapeutic field of neurology. The
round-the-clock analgesia. of Opana ER were more favourable than their rat- first is the excellent fit of neurology with
Secondly, the opioid prescriber market is ings of their previous opioid or of a placebo. Penwest’s technologies. Neurological disorders
under covered giving Endo the opportunity to Opana ER has also been studied in opioid- usually require chronic/ongoing therapy, Dr
achieve good penetration. The company has sig- naïve patients with chronic pain. In first time users, Baichwal, Penwest’s Chief Scientific Officer,
nificantly expanded its sales team to support side effects can be unpleasant enough to make the states, often self administered in non-clinical set-
Opana ER, adding some 220 new reps to create patient discontinue opiate therapy, and it was tings. This points clearly to the use of long-acting
a total sales force of about 600. important to know how this group of patients oral dosage forms. Maintaining constant plasma
Among long-acting pure oral opioids, oxy- would tolerate Opana ER. In a multi-center, ran- levels of an active compound while minimising
codone (Oxycontin®) is currently the most pre- domized, double-blind, parallel group trial, the dosing frequency is also beneficial in neurology
scribed. However, there is clearly room for an safety and efficacy of Opana ER were compared therapies, again pointing to long-acting formula-
alternative. Although Opana ER and Oxycontin with a placebo in 205 opioid-naïve patients with tions. “Penwest’s controlled-release technolo-
both interact on the µ-opiate receptor, patients moderate-to-severe chronic low back pain. Opana gies can help with compliance and safety by
respond differently to different compounds ER demonstrated a statistically significant (p < delivering a steady stream of medicine,” he notes.
within this class, meaning that the choice of an 0.0001) difference in pain scores between oxymor- The second addresses product sales and mar-
alternative improves treatment options. phone ER and a placebo over a 12-week treatment keting. Prescriptions for neurological products
Additionally, in long-term treatment, opiate period, during which the drug was administered are typically written by neurologists – a rela-
rotation (switching from one opioid to another twice daily. After titration to an effective and toler- tively small and identifiable group. Penwest has
similar product) overcomes the reduced effica- ated dose of Opana ER, adverse events incidence recognised that the type and size of sales force
cy that is often seen when one product is used was remarkably low over the 12 week double needed to address this market fits with the spe-
over an extended period. blind treatment period, with some of the common cialty pharma model and can be achieved more
Of perhaps more interest, is that Opana ER is opioid effects occurring but in a low frequency. quickly than that required to reach, for example,
a new, differentiated entrant. Oxycontin may be The FDA’s final approval of Opana ER was the large number of primary care practitioners.
an extended-release product, but marketing data a key milestone for Penwest and represented a Dr Baichwal details that the company has
indicates that in a substantial number of major step in advancing the company’s strategy adopted a three point strategy. Each aspect of
patients, it is being used three times per day of building a specialty pharmaceutical company this strategy is characterised by progressing
despite being indicated for twice-daily adminis- with a focus on developing compounds targeted experience and strengths.
Figure 2: Product pipeline showing current development status, and expected status for 2007 and 2008
The initial strategy has been to develop developed as a once daily tablet using ple – Torsemide ER offers great development
existing compounds that can be improved using Penwest’s Geminex. It provides extended potential. This fits with Penwest’s philosophy of
Penwest’s technologies. Penwest currently has release of the drug during the waking hours creating differentiated products. Torsemide ER
two named products in its portfolio that demon- when CHF patients need protection from is a clear demonstration of the benefit that its
strate this approach: Nalbuphine ER and absorbing dietary salt. technology can bring to an existing compound.
Torsemide ER. Chronically treated CHF patients typically In contrast to Nalbuphine ER, which Penwest
Nalbuphine ER is a controlled release formu- need to excrete between 150 mEq and 200 mEq plans, if approved, to market itself, Torsemide
lation of nalbuphine hydrochloride and incorpo- of sodium per day to prevent water retention ER, if approved, will be marketed by a partner.
rates Penwest’s drug delivery technology. weight gain that can lead to cardiac decompen- Clinical indications and development time-
Nalbuphine ER is designed to be taken as a sation. The current formulations of loop diuret- lines of these products, together with several other
twice-daily tablet. This formulation will have ics have short periods of action during which neurological compounds in Penwest’s pipeline,
plasma kinetics derived from both immediate most of the sodium excretion takes place. Short are summarised in figure 2.
release and controlled release components. durations can both leave the patient unprotected The second thread of Penwest’s strategy is
Nalbuphine hydrochloride is a synthetic opioid for long periods during the day, when sodium the development of external technology-based
agonist-antagonist analgesic of the phenanthrene retention is occurring via food, and create the products and the broadening of its technology
series and is currently only available as a sterile potential for large urinary volume diuresis after profile. The company is developing products
solution suitable for subcutaneous, intramuscu- drug ingestion, resulting in unpleasant side and accessing a portfolio of differentiated tech-
lar, or intravenous injection under the brand effects endangering compliance. nologies with specific applications in the neu-
name NUBAIN® and as a generic. Annual sales Commenting on clinical trial results released rology field. Importantly, this part of the strate-
of this product are approximately US$10 million at the end of 2005, Dr Thomas Sciascia said that gy is not limited to Penwest’s traditional field of
- constrained by the currently available formula- the company was “encouraged that the data sup- oral delivery. Feasibility studies are currently
tions and indications. If approved, Penwest ports the conclusion that torsemide can be for- underway with several pioneering non-oral
expects that oral Nalbuphine ER, which has suc- mulated and administered once daily in a man- delivery systems, the company has revealed.
cessfully completed Phase IIa trials, will com- ner that can result in a longer duration of action The final piece of the three-part strategy is
pete in the moderate to moderately severe pain than that provided by currently marketed brands the establishment of a proprietary portfolio of
market with drugs such as Tramadol®. of the drug. This difference could be significant neurological NCEs. Penwest is actively looking
The one non-neurological product in to congestive heart failure patients in a real to broaden its early stage drug development
Penwest’s pipeline is Torsemide ER. This is a world situation in which dietary sodium intake pipeline by investigating in-licensing NCEs in
controlled-release formulation of the loop- is large and sodium intake occurs throughout the selected areas of neurological therapeutics.
diuretic torsemide, and is currently marketed as waking hours.” Areas of interest include niche neurological
an immediate release oral formulation branded Retaining Torsemide ER when Penwest has diseases, where small molecule drug develop-
Demadex®, for the treatment of congestive decided to concentrate on neurologicals perhaps ment is still needed to treat conditions that are
heart failure (CHF). Torsemide ER has been raises some questions, but the rationale is sim- not adequately addressed with available medi-
cations. Penwest’s goal is to commercialize ensured optimal relations with Wall Street and CONCLUSION
these products, if approved, by building a spe- will further support in driving the business.
cialty sales force of its own or through out- The scientific team is also stronger. Amy Penwest is not alone in evolving from a technology
licensing arrangements. O’Donnel, MD, has been appointed to the new provider to a drug development company, attracted
position of Senior Director of Clinical by the growth that can be achieved via the special-
BUILDING THE Development joining Chief Medical Officer ty pharma business model. Companies such as
MANAGEMENT TEAM Thomas Sciascia, MD, and concentrating the Biovail and Alza have achieved success in trans-
company’s focus on therapeutic product forming themselves into high growth, value added
The refocused Penwest has built an optimal development. pharmaceutical companies developing important
management team, making several key appoint- Penwest has also preserved its drug delivery medicines that have a positive impact on patients.
ments to progress the business. Jennifer Good heritage. Dr Anand Baichwal, co-inventor of Penwest plans to capitalise on the opportunities that
was appointed to Chief Executive Officer in TIMERx and subsequent oral delivery technolo- lie ahead of them with their experienced manage-
June of 2006. With nine years of experience at gies, is the Company’s Chief Scientific Officer ment team, their expertise in drug delivery tech-
the company, Jennifer brings the necessary and Senior Vice-President of Licensing. nologies and their knowledge in drug development.
expertise, vision and energy to move Penwest Commenting on the company’s positive out- Penwest has built on its past achievements, com-
forward in its strategy. The appointment of look he says: “By late 2009, Penwest’s goal is to bining them with its current strength and expertise,
Benjamin Palleiko, a former investment banker, be a true development-focused specialty phar- and is poised for a new level of growth through a
to Senior Vice President, Corporate maceutical company, selling and marketing its diverse portfolio of drugs primarily targeted at
Development and Chief Financial Officer has own portfolio of neurology products.” treating diseases of the nervous system.
Oral controlled release technology Dual-delivery system which can Releases drug at the desired time
based on a natural gum matrix. release drugs or isomers at two and site in the body to coincide
different rates. with the body’s circadian rhythm
TIMERx achieves a variety of release
pattern or to allow drugs to be
profiles (First order, Zero order, To achieve the unique release profiles
delivered to different sites within
Burst CR, etc) for a wide range of different custom granulations are made
the GI tract.
drugs, accomodating even the most for each drug component. The two
difficult actives. drugs are then compressed on a By administering drug at the optimal
standard bi-layer press. time after ingestion, SyncroDose can
TIMERx can be used in:
potentially improve the therapeutic
Geminex offers:
• Low to high dose drugs benefit of drugs or reduce the dose
• Rapid development times which can needed to provide a given therapeutic
• Insoluble to highly-soluble drugs effect. If a reduction in dose occurs, the
result in a speed-to-market advantage.
• Drugs with short half-life and/or side effects of the drug may also be
• Custom formulations are made for reduced or lessened in severity.
narrow therapeutic window.
each drug component to ensure
The technology is based on maximum therapeutic benefits. A SyncroDose tablet consists of an
acustomised, agglomerated inner core of drug and a surrounding
• Special equipment is not required; compression coating containing
hydrophilic complex that forms a
a standard bi-layer press is all that TIMERx® based materials (see below).
controlled-releasematrix upon
is required. Lag time is controlled by variations in
compression.
• Geminex-based products are more the two polysaccharides, xanthan gum
The matrix consists of two and locust bean gum, found in the
cost-effective than combination drug
polysaccharides, xanthan and locust TIMERx coating.
products thatare based on the
bean gum. Interactions between these
application of multiparticulate
components in an aqueous
technologies.
environment form a tight gel with a
slowly-eroding core. Geminex can deliver a medication that
is therapeutically superior to its
individual components.
/
Oral Delivery Oct 06 18/1/07 20:19 Page 11
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DRUG ABSORPTION IN THE UPPER ') TRACT
In years gone by, the pharmaceutical industry has overlooked or dismissed combination products,
save but a few of the most obvious, straighforward applications. In this article, Fred Miller,
CEO of InnerCap Technologies, outlines why the climate is now right for the full potential of
combination product development across the spectrum of therapeutic categories to be realised,
and how the technology to make this possible and commercially viable is now available.
Up until almost the very end of last century, and proven popular with patients. As a result,
combination products essentially remained on physicians are becoming more accepting.
the periphery of pharmaceutical development. Furthermore, there is a positive feedback effect
There was no wholesale argument against the whereby, as combination products become more
concept of fixed-dose combinations. It was common, physicians are more familiar with
more the case that there was nothing much moti- their benefits, more comfortable with using
vating the sector towards their development. them, and therefore increasingly likely to pre-
There were a few exceptions where a fixed- scribe them. Indeed, as the merits of combina-
dose combination was the obvious (or only) tion products are revealed, groups of specialist
approach, such as the combinations of hor- medical professionals are now calling for the
mones in oral contraceptive pills, and levodopa development of combinations in certain applica-
combined with a dopa decarboxylase inhibitor tions within their field.
for Parkinson’s disease. Otherwise, however, We have also seen definitive signs of regulato-
industry focus was squarely on producing as ry acceptance of combination products of late. As
many blockbuster NMEs as possible. stated above, regulators, while not actively
The regulatory authorities were not against, against combination, used to be rather passive.
but there were some questions about inflexible Nowadays they too are identifying applications
dosing regimens and identifying the source of where combinations are appropriate, and are
adverse events arising from combination actively promoting the development of combina-
medicines, so neither were they actively pro tions as the preferred option. For example, in May
combination products. Physicians were similar- 2004 the US FDA published a draft guidance doc-
ly ambivalent. Most were certainly not crying ument entitled: Fixed Dose Combination and Co-
out for combination products to be made avail- Packaged Drug Products for Treatment of HIV.
Fred H. Miller
able to them, but they had no serious grievance Its opening sentence reads, “This guidance is President
with the idea of combination products per se. intended to encourage sponsors to submit applica-
In recent years, however, the tide has begun tions to the FDA for approval of fixed-dose com-
T: +1 813 837 0796
to change quite sharply. The number of combi- bination and co-packaged versions of previously F: +1 813 837 0207
nation products reaching the market has begun approved antiretroviral therapies for the treatment E: fmiller@innercap.com
to accelerate, and several high profile combina- of HIV.” We will return to discuss this particular
tion brands are generating formidable revenues guidance in more detail later on in the article, but
INNERCAP Technologies Inc
for their developers. Indeed, there are now at the point to note here is that the regulators have 5420 Bay Center Drive, Suite 100
least twelve combination drug products taken a position on fixed-dose combinations, and Tampa
amongst the top-200 selling pharmaceuticals. its is unequivocally in favour of their continued FL 33609
USA
Such combination products have only development.
achieved success because they work. That is, So, it is clear that the trend is now well www.innercap.com
they have shown significant therapeutic benefit established, but why have combinations gained
InnerCap has developed an elegant approach • The ability to incorporate multi-phased • Smaller number of bottles to maintain.
which overcomes technological barriers such as materials • Less odour and unacceptable taste.
these, providing a simple and cost-effective Solids, powders, granules, crystals, hot • Capsules are preferred dosage form by most
development process for a wide variety of com- melts, pastes, gels, liquids, coated materials, patients.
binations. Its NovaCaps platform comprises a lipids, enrobed, softgels, nanomolecules, • Capsules are easier for most patients to
range of multi-phased, multi-compartmental beadlets, micro-encapsulated, encochleates, swallow.
capsule-based delivery systems. suspensions, emulsions and gases in a single • Non-gelatin capsules.
The principle of NovaCaps is shown by dosage form.
the photo in figure 1 (page 13), which shows • Incompatible drugs in a single dosage
how four individual compounds are com- Wider selection of drugs to work within sin- CONCLUSION
bined into one single NovaCaps dosage form. gle dosage form
The combination example consists of a high- • Multiple capsule shell materials The time for combination products has now
potency insoluble active compound in a lipid Multiple shell materials can be used in single come, and an effective formulation solution is
emulsion, a sustained-release tablet and a dosage form. now in demand. Not only can the NovaCaps
cocktail of two crystalline active materials. A • Multiple release profiles technology be applied to solve problems in the
combination of release profiles can be incor- Combine different release profiles such as development of standard oral combinations,
porated in the system. immediate, delayed, enteric, sustained and but it enables the rapid and cost-effective
In the development of combinations of one timed. development of advanced, highly differentiat-
soluble and one insoluble compound, capsules • Single Indication ed, innovative products.
containing substances in different physical Drugs combined to target one disease state or InnerCap is now actively engaged in seeking
phases can be utilised (see figure 2). NovaCaps side effects. partners with which to develop products and
can combine incompatible and compatible drugs • Multiple indications bring them to market. The company will consid-
utilizing different physical phases. Each com- Drugs combined to target separate disease er a range of transaction structures including
partment is sealed to prevent the medicaments states or organ systems. product licensing, co-promotions, distribution
from escaping and coming into contact with one • Ease of scale-up arrangements, royalty-based transactions and
another. If a compound is currently stable with- Modified existing equipment can be used to partnership arrangements.
in a capsule, stability problems are precluded in manufacture products. InnerCap’s philosophy is built around pro-
a multi-capsule application. • Fewer excipients viding solutions to patients, healthcare
As with any new combination drug project, Different phases can reduce number of excip- providers, physicians, and its R&D partners
a combination drug may not work in a specific ients in dosage. through the development of combination drug
dosage form due to incompatibility or other for- • Increased bioavailability through absorption therapies. We offer partners the benefit of a
mulation issues and an alternative delivery sys- Materials to increase bioavailability can be strong intellectual property position, in relation
tem will have to be identified. For instance, included in formulation. Poorly water soluble to the InnerCap delivery system and a range of
both bi-layer tablets and multi-compartment drugs can be significantly enhanced. delivery targets.
capsules have specific benefits associated with • Increased stability
the dosage form. If the combination product Reduced oxidation through use of antioxi- REFERENCES
will contain incompatible or multi-phase com- dants protecting actives. Reduced moisture
pounds, multi-compartment capsules can make sensitivity by use of lipophilic matrix. 1. Bell D, Wyne K: “Symposium on diabetes:
a project possible that may otherwise fail in a use of fixed-dose oral combinations.”
bi-layer tablet. This new development may Furthermore, products presented in this Postgraduate Medicine, 2006, Vol 119, No 2
allow projects that have failed in the past to delivery system can help pharmaceutical mar-
become viable projects and dramatically keting teams build a compelling case for an 2. Bailey C: “Whence and whither the fixed-dose
increases the possibilities when working with attractive solution. Some of the aspects of the combination?” Diabetes and Vascular Disease
different combinations. NovaCaps-enabled product’s profile that could Research, 2005, Vol 2, Issue 2, pp 51-53
Also, multi-compartment capsules can be included are summarised here:
accelerate the development of a combination 3. Quan A, Chavanu K, Merkel J: “A review of
product and proceed to clinical trials by min- • Fewer pills to be administered. the efficacy of fixed-dose combinations olmesar-
imising the formulation development of a com- • Reduces number of drugs prescribed by tan medoxomil/hydrochlorothiazide and amlodip-
bination tablet project. This allows a combina- physician. ine besylate/benazepril in factorial design stud-
tion product to enter clinical trials and acceler- • Reduces liability issues relating to prescrib- ies.” American Journal of Cardiovascular Drugs,
ate the process to determine if the new product ing physician. 2006, Vol 6, No 2, pp 103-113
achieves the desired therapeutic effects in the • Drugs are administered in correct sequence.
trial group. This approach can save millions of • Timing of regimen correctly adhered to 4. du Toit LC, Pillay V, Danckwerts MP:
dollars in development costs, and a first-to- by provider. “Tuberculosis chemotherapy: current drug
market advantage can be the factor that decides • Greater consumer appeal. delivery approaches.” Respiratory Research,
the success or failure of a multi-million dollar • Aid in drug identification and product differ- 2006, Vol 7, No 1, p 118
product in the marketplace. entiation.
Novacaps offers extensive advantages and • Create positive psychological response 5. Langford RM: “Pain management today-what
opens up a variety of opportunities in the devel- through colour and visual product appeal. have we learned?” Clinical Rheumatology,
opment of novel combinations. These include: • Simplicity of regimen reduces mistakes. 2006, Vol 25, Supplement 7, pp 2-8
Incorporated into 130 marketed products generating an estimated US$2 billion in sales annually
by 2004, the first generation of orally dissolving tablet technologies is well established in the
global pharmaceutical market. Here, Steve Ellul, Business Development Director at Eurand,
explains how second-generation ODT technologies, which overcome technical challenges and
address needs not met by the first generation, are now poised to enter the global market, and
Eurand’s Advatab is in the prime position.
“We are delighted that GSK has chosen Eurand result of these benefits. A few key facts and fig-
for this important project. We believe it further ures are summarised here as examples:
confirms our market leading position in the fields
of taste-masking and oral disintegrating tablets. • More than half of all medicines are given oral-
“The combination of our Microcaps™ and ly, yet 30% of patients find swallowing diffi-
AdvaTab® technologies has received an enthusi- cult; in particular children and the elderly.
astic reception from industry leaders such as • Some medical conditions cause dysphagia.
GSK and we are currently in advanced negotia- • In one survey, 88% of patients indicated that
tions with companies in Japan, Europe and the they would prefer ODT formulations over tra-
USA for a range of different products.” ditional oral dosage forms.
This was Gearóid Faherty, Eurand’s Chief • In a study in 4,000 depressed patients, con-
Executive Officer commenting just last October ducted by Organon and presented at the
on the news that GlaxoSmithKline had entered American Psychiatric Association, two thirds
into a development and licensing agreement to preferred the ODT formulation of Remeron to
use Eurand’s Microcaps taste-masking system the conventional tablet formulation, and half
and AdvaTab oral disintegrating tablet (ODT) said that they were more likely to comply with
technology for the development of a new for- the ODT product.
mulation of a GSK compound. • A 2003 poll conducted by Harris International
The question is: why AdvaTab and why and sponsored by Schwarz Pharma suggested
Eurand? What exactly did Eurand bring to the that 40% of American adults have experienced
table that others did not? It is of course impos- difficulty swallowing pills. As a result, 14%
Steve Ellul
sible to answer this in a single sentence or even delayed taking their medication, 8% skipped Business Development Director
a paragraph, but there are several distinct rea- doses and 4% discontinued treatment. Less
sons why pharmaceutical companies might than 25% discussed the swallowing difficulty
T: +39 02 95428281
well wish to make Eurand their partner; and with their doctor. E: Steve.Ellul@eurand.com
these are set out in detail throughout the
remainder of this article. Yet the advantages of ODT formulations are
Eurand
Let’s begin by examining the market briefly. not only for patients. The suitability of ODT Via M. Luther King, 13
ODTs provide: convenient dosing; inconspicu- technology for application in lifecycle manage- 20060 - Pessano con Bornago
ous drug administration without the need for ment, market expansion and product differentia- Milan
water; enhanced compliance and enhanced effi- tion means that pharmaceutical companies that Italy
cacy. There is a wealth of data which suggests choose to develop ODT versions of their prod- www.eurand.com
that a significant demand for ODTs exists as a ucts can derive considerable commercial benefit.
needs. The core requirements for an ODT sys- PHASING OUT INDUCER
MATERIAL TO BE COATED
• Pleasant taste and mouth-feel without grittiness
• Adequate speed of disintegration (less than 30
seconds) Figure 1: The Microcaps® coacervation process – microencapsulation by
• Good drug-loading capacity phase separation
• Mechanical strength of tablet that allows stan-
dard packaging In first-generation ODT development, com- approach, physical barrier methods, include
• Ability to manufacture the tablet on standard promise was the name of the game. When dis- spray drying, fluid bed coating and coacervation.
lines with minimal involvement of expensive cussing and assessing a second-generation ODT, These techniques coat particles of the active
specialised equipment it is important to look at how it measures up compound so that they do not come into direct
against the various requirements together, rather contact with the taste receptors on the tongue.
It is of course possible to identify first-genera- than analysing their performance against each Eurand’s Microcaps taste-masking technol-
tion technologies that meet the needs above – criterion in isolation. The remit for the next gen- ogy uses coacervation, a versatile, precise coat-
but the difficulty is finding a single technology eration of ODT systems is for a single technolo- ing technique that encapsulates individual drug
that ticks all of these boxes. When it came to gy to meet all of the requirements upon it. particles, completely enveloping them to
choosing a first-generation ODT technology, AdvaTab is that technology. It has already achieve superior taste-masking properties. The
pharmaceutical companies had to make their reached the market in Japan, and AdvaTab prod- coacervation process, which is outlined
selection on the basis that any single OTD ucts are due to be launched in 2007 in the US, schematically in figure 1, places a uniform
would satisfy perhaps one or two requirements, and in Europe in 2008. coating of polymeric membranes of varying
but at the expense of others. Taste-masking ability, although not the only thicknesses and degrees of porosity directly
One simple example of how one characteris- important quality of an ODT, is certainly at the onto the dry crystals or granules, creating parti-
tic had to be played off against the other is that crux of the issue. Firstly, the proper engineering cles, typically 150-300 microns in size, suitable
of disintegration time and drug loading. Rapid of the taste-masked drug particle is the first step for incorporation into an ODT.
disintegration was often achieved by making the in the creation of an ODT product. Secondly, Microcaps has been used to taste-mask a
tablet highly porous. However it is clear that as developing an effective approach to taste-mask- wide range of extremely poor-tasting drugs,
porosity (the proportion of the dosage form that ing that does not impinge on the other charac- including zolpidem for insomnia, sumatriptan
comprises nothing more than air) increases, the teristics of the tablet has presented a huge tech- for migraine, ranitidine for GERD, and ceti-
amount of space in the tablet remaining for the nical challenge in ODT R&D. Third, although rizine for allergic rhinitis, as well as theo-
active drug substance and excipients decreases first-generation ODT development was all about phylline, ibuprofen, acetaminophen and pseu-
accordingly. Furthermore, increased porosity compromise, the taste-masking element pro- doephedrine. Eurand’s taste-masked actives
can make the tablet mechanically weaker and vides the least wiggle room. If patients can’t are incorporated into products such as
more friable, to the extent that additional spe- bear even to put the tablet in their mouths Novartis’s Triamcinic Softchews®, Whitehall
cialised packaging such as peel-off blister pack- because it is so face-twistingly bitter, the tech- Robins’ Children’s Chewable Advil®, Rulid®
aging is required. nology has surely fallen at the first hurdle – (roxithromycin), and the Benadryl® line of
Taste-masking provides another example of especially since ODTs are a means of improving products from Pfizer.
how difficult it is to tick all the boxes. the patient experience in order to make a prod- Microcaps goes further than simply the pro-
Ineffective taste-masking technology means that uct more attractive and increase compliance. vision of effective taste-masking. As anyone
the dose of bitter active ingredient has to be kept Eurand has a strong heritage in the provision involved in drug development will know, the
small, limiting the application of the technology of first-class taste-masking technology. There real challenges only become apparent once
to low-dose products. The obvious way of are two broad approaches to masking the bitter work on a specific product begins, and so the
ensuring effective taste-masking is to use a taste of a drug. Organoleptic methods typically true superiority of Microcaps is best highlighted
thicker coating, but this often results in poor dis- employ strong flavours and/or sweeteners to by an example of its application in a real-world
solution in the stomach. overpower the drug’s taste. The second product development scenario.
CONCLUSION
One of the most difficult technical challenges in drug delivery is the successful development of
large-molecule and protein therapeutics as orally administered formulations. It also promises
some of the richest rewards. Here, Emisphere Technologies’ Director of Corporate Development,
Ms. Bavani Shankar, shows that Emisphere is closing in fast on drug delivery’s true Holy Grail.
There is no doubt that oral administration of agents have no known pharmacological activity
drugs is the “Holy Grail” sought after by the themselves at the intended clinical dose levels.
pharmaceutical industry. This method of admin- The unique feature of this technology is that
istration is patient friendly and improves patient it facilitates oral delivery without chemical
compliance. However, this route is not available modification of the drug. The interaction
to large molecules and proteins, thereby limiting between the EMISPHERE® delivery agents and
their potential for a wide range of therapeutic the drug molecule is non-covalent.
indications. Some of the major challenges to Although the mechanism of action has not
delivering these molecules are: been fully elucidated, studies conducted to date
show that these delivery agents transiently alter
• Degradation of drugs by the high acid content the physicochemical properties of the drug
and digestive enzymes molecules (e.g. hydrophobicity), allowing the
• Poor absorption of drugs through epithelial drug molecule to be more readily transported
membrane across the GI, along with the delivery agent.
• Transition of some drugs to an insoluble form Once the molecules cross the epithelial cells, the
at physiological pH levels, effectively slowing delivery agent disassociates from the drug
the absorption rate. molecule, returning the molecule to its thera-
peutically active state. Figure 1 summarises a
The drug delivery industry is comprised of proposed mechanism for the delivery agents.
companies seeking novel methods to deliver Additional studies conducted on the pathway
large molecules orally and improving oral of absorption have shown that the transport is by
absorption of small molecules including, but passive transcellular diffusion and maintains
not limited to: the pro-drug concept, where the cell integrity.
drug is chemically modified; lipid based sys- The eligen® technology does not disrupt the
tems; and other novel delivery systems. This tight junctions between the cells, as is the case
article will focus on the oral delivery of thera- with classic penetration enhancers.
peutic molecules utilising Emisphere’s novel Author: Ms. Bavani Shankar
Director, Corporate Development
drug delivery technology, eligen®. A TECHNOLOGICAL PERSPECTIVE:
THE ELIGEN® TECHNOLOGY The technology is broadly applicable for dif- T: +1 914 347 2220
F: +1 914 347 2498
ferent types of molecules varying in molecular
E: businessdevelopment@emi-
The eligen® technology, developed by size (up to 100,000 Daltons) and structure. sphere.com
Emisphere Technologies Inc, is a platform tech- Using this technology, Emisphere Technologies
nology based on the use of a library of over 4000 has shown the delivery of therapeutic molecules
Emisphere Technologies Inc
synthetic, proprietary chemicals known as “carri- in several clinical studies, some of which are 765 Old Saw Mill River Road
ers” or “delivery agents”. These delivery agents described below. Tarrytown
enable or enhance the absorption of therapeutic Small Molecules: The pharmacokinetic pro- NY 10591
USA
agents across biological membranes, such as those file of molecules orally delivered using the eli-
of the GI tract, thereby allowing these molecules to gen® technology is typically characterised by a www.emisphere.com
enter into the systemic circulation. The delivery rapid onset of action. This feature has been used
In a drug delivery industry where marketed products and a broad technology platform are
crucial, CIMA LABS INC today is in an excellent position. Some time ago, it was a company
that simply provided orally disintegrating tablet technology. Today CIMA offers a range of oral
drug delivery systems the majority of which, being utilised in commercially available products,
are thoroughly market-proven.
Products are everything in drug delivery today; saliva, Fentora's delivery system generates a
and rightly so. For a delivery technology is reaction leading to the release of carbon diox-
essentially valueless without a pharmaceutical ide. It is believed that transient pH changes
product application. It is therefore appropriate accompanying this reaction may optimise how
that in this article, we describe CIMA’s drug well the tablet dissolves and how quickly the
delivery technology offering in the context of the medicine passes across the buccal mucosa.
many products in which they have been applied. In placebo-controlled clinical trials, patients
In September 2006, Cephalon, CIMA’s par- treated with Fentora showed a statistically sig-
ent company, announced the US FDA approval nificant improvement on the primary end point,
of Fentora®, its buccal tablet formulation of fen- the Sum of Pain Intensity Differences (SPID30)
tanyl, which uses CIMA’s OraVescent® technol- (p<0.01) and some patients experienced clinical-
ogy. Fentora is the first and only buccal tablet ly significant decreases in pain intensity and
indicated for the management of breakthrough greater pain relief within 15 minutes, the first
pain in opioid-tolerant cancer patients. time point measured. In addition, pharmacoki-
Thanks to the unique delivery system, netic data indicate that systemic exposure to fen- Dr Richard J. Welter
Fentora is protected by a robust patent estate tanyl occurred earlier and was approximately Vice President, Business
until 2019. Yet the benefits that OraVescent 30% greater with Fentora than with Cephalon’s Development
brings to the product are more than just com- ACTIQ® (oral transmucosal fentanyl citrate). T: +1 952 947 8748
mercial. The therapeutic efficacy of Fentora is ACTIQ is another example of a marketed F: +1 952 947 8711
rooted in the way it is delivered. product that incorporates CIMA’s delivery sys- E: richard.welter@cimalabs.com
Breakthrough pain, a common component of tems. CIMA’s Oral Transmucosal Delivery
chronic pain, is characterised by its rapid onset, System (OTS®) – the “lozenge-on-a-stick” tech- Dr Derek Moe
intensity, and relatively short duration. nology – allows easy patient control of the rate Group Director, CIMA R&D
Conventional short-acting oral opioids, which are of drug delivery. The active ingredient is admin-
T: +1 763 488 4751
swallowed and absorbed in the gastrointestinal istered by rotating and dissolving it against the F: +1 763 488 4770
tract, can take up to 30-45 minutes to take effect. oral mucosa, thus providing a simple mecha- E: derek.moe@cimalabs.com
With Fentora, thanks to OraVescent, approxi- nism for the patient to dose to effect.
mately half of the medicine is absorbed directly Fentora and ACTIQ have of course been CIMA LABS INC
across buccal mucosa, and into the bloodstream developed inside the Cephalon family. 10000 Valley View Road
more quickly than if it were swallowed and bro- However, CIMA’s operations extend outside Eden Prairie
ken down by the liver in the gastrointestinal tract. Cephalon. The company has a variety of collab- MN 55344
USA
The sugar-free Fentora tablet is placed orations with pharmaceutical partners. For
between the upper cheek and gum above a rear example, in June 2006, the US FDA approved www.cimalabs.com
molar tooth. When it comes into contact with BioMarin and Alliant Pharmaceuticals’ Orapred
the
a d va n tag e s
of multi-phase, multi-compartment capsules are clear
5420 Bay Center Drive • Suite 100 • Tampa, FL 33609-3425 USA • (813) 837-0796 • www.innercap.com • fmiller@innercap.com
Oral Delivery Oct 06 18/1/07 20:20 Page 25
COMPANY PROFILES
11th Annual
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It all starts in the boardroom. There comes a time in every product's lifecycle when a strategic
decision must be made. As a leader in drug delivery, CIMA LABS can help you keep your promise
to your company by fulfilling our promise to you. Whether utilizing our orally disintegrating tablet
technologies or choosing one of our newer advancements, you can be confident that CIMA LABS
will deliver a fully commercialized product.
Let us bring our best thinking to your table. We think you, and your organization, will like the results.
cimalabs.com
952.947.8700
Oral Delivery Oct 06 18/1/07 20:20 Page 28