Pharmaceutical formulation, in pharmaceutics, is the

process in which different chemical substances, including the active drug, are combined to produce a final medicinal product.

Stages and timeline

Formulation studies involve developing a preparation of the drug which is both stable and acceptable to the patient. For orally taken drugs, this usually involves incorporating the drug into a tablet or a capsule. It is important to appreciate that a tablet contains a variety of other substances apart from the drug itself, and studies have to be carried out to ensure that the drug is compatible with these other substances. Preformulation involves the characterization of a drug's physical, chemical, and mechanical properties in order to choose what other ingredients should be used in the preparation. In dealing with protein pre-formulation, the important aspect is to understand the solution behavior of a given protein under a variety of stress conditions such as freeze/thaw, temperature, shear stress among others to identify mechanisms of degradation and therefore its mitigation.[1]

Formulation studies then consider such factors as particle size, polymorphism, pH, and solubility, as all of these can influence bioavailability and hence the activity of a drug. The drug must be combined with inactive additives by a method which ensures that the quantity of drug present is consistent in each dosage unit e.g. each tablet. The dosage should have a uniform appearance, with an acceptable taste, tablet hardness, or capsule disintegration. It is unlikely that formulation studies will be complete by the time clinical trials commence. This means that simple preparations are developed initially for use in phase I clinical trials. These typically consist of hand-filled capsules containing a small amount of the drug and a diluent. Proof the long-term stability of these formulations is not required, as they will be used (tested) in a matter of days. Consideration has to be given to what is called the drug load - the ratio of the active

drug to the total contents of the dose. A low drug load may cause homogeneity problems. A high drug load may pose flow problems or require large capsules if the compound has a low bulk density. By the time phase III clinical trials are reached, the formulation of the drug should have been developed to be close to the preparation that will ultimately be used in the market. A knowledge of stability is essential by this stage, and conditions must have been developed to ensure that the drug is stable in the preparation. If the drug proves unstable, it will invalidate the results from clinical trials since it would be impossible to know what the administered dose actually was. Stability studies are carried out to test whether temperature, humidity, oxidation, or photolysis (ultraviolet light or visible light) have any effect, and the preparation is analysed to see if any degradation products have been formed. It is also important to check whether there are any unwanted interactions between the preparation and the container. If a plastic container is used, tests are carried out to see whether any of the ingredients become adsorbed on to the plastic, and whether any plasticizers, lubricants, pigments, or stabilizers leach out of the plastic into the preparation. Even the adhesives for the container label need to be tested, to ensure they do not leach through the plastic container into the preparation.

Oral formulations
The way a drug is formulated can avoid some of the problems associated with oral administration. Drugs are normally taken orally as tablets or capsules. The drug (active substance) itself needs to be soluble in aqueous solution at a controlled rate. Such factors as particle size and crystal form can significantly affect dissolution. Fast dissolution is not always ideal. For example, slow dissolution rates can prolong the duration of action or avoid initial high plasma levels. Treatment of active ingredient by special way as spherical crystallization[2] can have some advantages for drug formulation.

Tablet form
Main article: Tablet A tablet is usually a compressed preparation that contains:

5-10% of the drug (active substance); 80% of fillers, disintegrants, lubricants, glidants, and binders; and 10% of compounds which ensure easy disintegration, disaggregation,

and dissolution of the tablet in the stomach or the intestine. The disintegration time can be modified for a rapid effect or for sustained release. Special coatings can make the tablet resistant to the stomach acids such that it only disintegrates in the duodenum, jejunum and colon as a result of enzyme action or alkaline pH. Pills can be coated with sugar, varnish, or wax to disguise the taste. Some tablets are designed with an osmotically active core, surrounded by an impermeable membrane with a pore in it. This allows the drug to percolate out from the tablet at a constant rate as the tablet moves through the digestive tract.

Capsule form
: Capsule (pharmacy) A capsule is a gelatinous envelope enclosing the active substance. Capsules can be designed to remain intact for some hours after ingestion in order to delay absorption. They may also contain a mixture of slow- and fast-release particles to produce rapid and sustained absorption in the same dose.

Topical medication forms

Main article: Topical

Cream - Emulsion of oil and water in approximately equal proportions.

Penetrates stratum corneum outer layer of skin well.

Ointment - Combines oil (80%) and water (20%). Effective barrier

against moisture loss.

Gel - Liquefies upon contact with the skin. Paste - Combines three agents - oil, water, and powder; an ointment in

which a powder is suspended.

Powder - they were finely subdivide substances, which are used as

antiseptic and prurient action.

See also

Formulations General aspects of formulations, its manipulation and Formulation science Pesticide formulation Medicinal chemistry
o o

calculations.

Dosage form Drug delivery

Excipient

o o o

Drug design Drug development Drug discovery

Galenic formulation

A lubricant (sometimes referred to as "lube") is a substance (often a liquid) introduced between two moving surfaces to reduce the friction between them, improving efficiency and reducing wear. It may also have the function of dissolving or transporting foreign particles and of distributing heat. A lubricant's ability to lubricate moving parts and reduce friction is the property known as lubricity. One of the single largest applications for lubricants, in the form of motor oil, is protecting the internal combustion engines in motor vehicles and powered equipment. Typically lubricants contain 90% base oil (most often petroleum fractions, called mineral oils) and less than 10% additives. Vegetable oils or synthetic liquids such as hydrogenated polyolefins, esters, silicones, fluorocarbons and many others are sometimes used as base oils. Additives deliver reduced friction and wear, increased viscosity, improved viscosity index, resistance to corrosion and oxidation, aging or contamination, etc.

Purpose
Lubricants perform the following key functions.

Keep moving parts apart Reduce friction Transfer heat Carry away contaminants & debris Transmit power Protect against wear Prevent corrosion Seal for gases Stop the risk of smoke and fire of objects

[edit] Keep moving parts apart

Lubricants are typically used to separate moving parts in a system. This has the benefit of reducing friction and surface fatigue together with reduced heat generation, operating noise and vibrations. Lubricants achieve this by several ways. The most common is by forming a physical barrier i.e. a thin layer of lubricant separates the moving parts. This is termed hydrodynamic lubrication. In cases of high surface pressures or temperatures the fluid film is much thinner and some of the forces are transmitted between the surfaces through

Reduce friction
Typically the lubricant-to-surface friction is much less than surface-to-surface friction in a system without any lubrication. Thus use of a lubricant reduces the overall system friction. Reduced friction has the benefit of reducing heat generation and reduced formation of wear particles as well as improved efficiency. Lubricants may contain additives known as friction modifiers that chemically bind to metal surfaces to reduce surface friction even when there is insufficient bulk lubricant present for hydrodynamic lubrication, e.g. protecting the valve train in a car engine at startup.

Transfer heat
Both gas and liquid lubricants can transfer heat. However, liquid lubricants are much more effective on account of their high specific heat capacity. Typically the liquid lubricant is constantly circulated to and from a cooler part of the system, although lubricants may be used to warm as well as to cool when a regulated temperature is required. This circulating flow also determines the amount of heat that is carried away in any given unit of time. High flow systems can carry away a lot of heat and have the additional benefit of reducing the thermal stress on the lubricant. Thus lower cost liquid lubricants may be used. The primary drawback is that high flows typically require larger sumps and bigger cooling units. A secondary drawback is that a high flow system that relies on the flow rate to protect the lubricant from thermal stress is susceptible to catastrophic failure during sudden system shut downs. An automotive oil-cooled turbocharger is a typical example. Turbochargers get red hot during operation and the oil that is cooling them only survives as its residence time in the

system is very short i.e. high flow rate. If the system is shut down suddenly (pulling into a service area after a high speed drive and stopping the engine) the oil that is in the turbo charger immediately oxidizes and will clog the oil ways with deposits. Over time these deposits can completely block the oil ways, reducing the cooling with the result that the turbo charger experiences total failure typically with seized bearings. Non-flowing lubricants such as greases & pastes are not effective at heat transfer although they do contribute by reducing the generation of heat in the first place.

[edit] Carry away contaminants and debris

Lubricant circulation systems have the benefit of carrying away internally generated debris and external contaminants that get introduced into the system to a filter where they can be removed. Lubricants for machines that regularly generate debris or contaminants such as automotive engines typically contain detergent and dispersant additives to assist in debris and contaminant transport to the filter and removal. Over time the filter will get clogged and require cleaning or replacement, hence the recommendation to change a car's oil filter at the same time as changing the oil. In closed systems such as gear boxes the filter may be supplemented by a magnet to attract any iron fines that get created. It is apparent that in a circulatory system the oil will only be as clean as the filter can make it, thus it is unfortunate that there are no industry standards by which consumers can readily assess the filtering ability of various automotive filters. Poor filtration significantly reduces the life of the machine (engine) as well as making the system inefficient.

Transmit power
Lubricants known as hydraulic fluid are used as the working fluid in hydrostatic power transmission. Hydraulic fluids comprise a large portion of all lubricants produced in the world. The automatic transmission's torque converter is another important application for power transmission with lubricants.

Protect against wear Lubricants prevent wear by keeping the moving parts apart.
Lubricants may also contain anti-wear or extreme pressure additives to boost their performance against wear and fatigue.

Prevent corrosion
Good quality lubricants are typically formulated with additives that form chemical bonds with surfaces to prevent corrosion and rust.

Seal for gases

Lubricants will occupy the clearance between moving parts through the capillary force, thus sealing the clearance. This effect can be used to seal pistons and shafts.

Types of lubricants
In 1999, an estimated 37,300,000 tons of lubricants were consumed worldwide.[1] The majority was for automobiles, but other industrial, marine, and metal work applications are also big consumers of lubricants. Although air and other gas-based lubricants are known, e.g. in fluid bearings), liquid and solid lubricants dominate the market, especially the former. Lubricants are generally composed of a majority of base oil and a minority of additives to impart desirable characteristics. Although generally lubricants are based on one type of base oil or another, it is quite possible to use mixtures of the base oils to meet performance requirements.

A glidant is a substance that is added to a powder to improve its flowability. A glidant will only work at a certain range of concentrations. Above a certain concentration, the glidant will in fact function to inhibit flowability (Which means that there's a critical concentration to be used if increasing powder's flowability is intended with respect to the glidant and the powder properties). In tablet manufacture, glidants are usually added just prior to compression.

Examples of glidants include magnesium stearate, Aerosil (colloidal silicon dioxide), starch and talc.

Mechanism Of Action
A Glidant's effect is due to a counter-action to factors resulting in poor flowability of powders. For instance, correcting surface irregularity, reducing interparticular friction & decreasing surface charge. The result is a decrease in the angle of repose which is an indication of an enhanced powder's flowability. In processed animal foods, a filler is an ingredient added to provide dietary fiber, bulk or some other non-nutritive purpose. Dietary fiber acts as a calming base for forming the stool in the colon, and it should help develop good fecal consistency, in addition to other health benefits such as reduced blood sugar uptake.

Capsule (pharmacy)
In the manufacture of pharmaceuticals, encapsulation refers to a range of techniques used to enclose medicines in a relatively stable shell known as a capsule, allowing them to, for example, be taken orally or be used as suppositories. The two main types of capsules are: Hard-shelled capsules, which are normally used for dry, powdered ingredients or miniature pellets (also called spheroids that are made by the process of Extrusion and Spheronization - Spheronization is a trade mark of Caleva Process Solutions) or tablets; Soft-shelled capsules, primarily used for oils and for active ingredients that are dissolved or suspended in oil.