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PHARMACEUTICAL SCIENCES
http://doi.org/10.5281/zenodo.1069757
Please cite this article in press as P. Shashidhar et al., Preparation, Characterization and In-Vitro Evaluation of
Probenecid: A Prototypical Uricosuric Agent In To Extended Release Microspheres, Indo Am. J. P. Sci, 2017;
4(12).
INTRODUCTION [1]:
Oral drug release is for the most part ideal and
appropriate preference since the oral means offer
highest active surface area amongst the entire drug
release method for administration of a range of drugs.
The magnetism of these dosage forms is owing to
knowledge to toxicity and uselessness of drugs once
administered by oral common technique in the type
of pills as well as capsules. Generally usual dosage
form produces extensive sort of difference in drug
concentration within the blood flow in addition to
tissues by resulting unwanted toxicity and poor
efficacy.
drug release method. Absorption of the unionized cases. Preferably, the drug ought to have half-life of
drugs are fine while penetration of ionized drug is 3-4 hours for formulation of drug delivery system.
insignificant as the absorption time of ionized drug is
3-4 times not as much as that of the unionized drug. Therapeutic indicator
The pKa variety for acidic drug whose ionization is Medicines with small therapeutic index are
pH responsive is around 3.0-7.5 and pKa array for inappropriate for inclusion in controlled discharge
basic drug whose ionization is pH aware is formulations. If the technique be unsuccessful in the
approximately 7.0-11.0 are idyllic for most favorable body, dose dumping might take place, which leads to
optimistic absorption. toxicity.
quantity in the right phase of time there by causing Carbohydrates: Agarose, Chitosan,Starch
small toxicity and negligible side effects. There are a Proteins: Albumin, Collagen and Gelatin
variety of move towards delivering a therapeutic
material to the intentional location in a sustained Chemically personalized carbohydrates: Poly
controlled discharge style. One such advance is by dextran, Poly starch.
using microspheres as transporter for drugs. 2. Synthetic polymers are of two kinds.
Microspheres are typically liberated flowing fine
particles consisting of protiens or synthetic polymers Biodegradable polymers
which are biodegradable in character and preferably E.g. Lactides, Glycolides & their copolymers, Poly
having a particle size not as much of as 200 m. anhydrides, Poly alkyl cyano acrylates.
amount of the drug Probenced was filled into the 1mg/ml(1000g/ml) which was set apart as "stock
sealed capillary tube. Then this tube was tied to the course of action A".
tube having the oil phase in such that the sealed part
of the capillary containing the drug was dipped into 2. From the stock game plan A, 1ml was pipette out
the oil. Gently the oil bath was heated. When powder in 10ml test tube and the last volume was made upto
starts melting, the heating was stopped and the 10ml with methanol. The came to fruition game plan
temperature is noted down at which the drug melts had the gathering of 0.1mg/ml (1000 stock game plan
starts melting. A, 1ml was pipette out in 10ml test tube and the last
volume was made up to 10ml with methanol. The
Determination of Partition Coefficient [7]: occurred course of action had the gathering of
The partition coefficient of the drug Probenced was 0.1mg/ml (100g/ml) which was named as "stock
known by using equal volumes of 1-octanol and plan B". This stock course of action B is used as
aqueous solution in a separating funnel. working stock response for moreover consider.
Encourage weakening were set up from a comparable
For water soluble drugs, drug solution was prepared game plan.
in distilled water, and for water insoluble drugs, drug
solution was prepared using 1-octanol. Course of action of standard work plan:
From the stock course of action B, advance
1-octanol (100 ml) is added to the equal volume of weakenings were made with methanol in 10ml test
the drug solution prepared in separating funnel by tube to get the game plans in the extent of 2-10g/ml
using distilled water and the solutions were allowed center and absorbance was recorded at 247nm against
to separate with shaking at irregular intervals. Then sensible clear using UV-Spectrophotometer.
the drug solution was separated and assayed for drug Modification twist of absorbance against obsession
content. was plotted.
D_ (t) = M/Vt
Method followed is phase separation emulsion
technique: Wherein M mass of powder
1) Initially prepare a polymer solution i.e.,40mg Vt- tapped quantity of powder.
sodium alginate in 20ml water taken in a 50ml
beaker. The angle of repose
2) To this slowly add 20mg of drug (probenced). Its far the maximum perspective viable among the
3) Allow it for stirring, under a mechanical stirrer for floor of the pile of powder and the horizontal aircraft.
at least 10 15min. The microspheres have been allowed to float thru the
4) Due to excessive stirring, bubbles will be formed funnel constant to a stand at specific peak. The
in the solution which can be removed by addition of attitude of repose becomes then calculated by using
5mg S.L.S. under a digital ultra sonicator. measuring the height and radius of the heap of
5) Then in another beaker take 5%Cacl2 (i.e.; 5gm in microspheres shaped. Care turned into taken to see
100ml H2O) and mix it properly to figure a that the microspheres align and roll over each
consistent solution. different via the edges of the funnel.
6) Then with the aid of a needle, add the prepared
polymer solution drop wise into the Cacl2 solution. It is given through - Tan= h/r
7) Transparent micro beads can be observed in the
cacl2 solution, these micro beads are nothing but the = tan ^ (-1) h/r.
microspheres.
8) Filter the solution to separate the microspheres.
Where =angle of repose;
9) The separated microspheres are kept a side till 15-
20 min for drying in a tray drier at 60 degrees until h=height in cm and r = radius in cm
all the moisture is evaporated.
10) Add Titanium dioxide to the above formulated Compressibility Index:
microspheres to make them stable for a longer It indicates powder flow properties. It is expressed in
duration. % and is given by
11) These microspheres are then evaluated and
characterized for their quality and in-vitro dissolution
studies.
release was considered using the equation obtained calibrations curve was drawn with absorbance values
from a standard curve. on y-axis and concentrations on x-axis where R2
value was found to be 0.998.
Determination of release rate kinetics:
Stability studies:
Optimized trial will be allowed to keep in force
degradation studies or accelerated stability studies at
60oC and 60%RH, for period of one month.
FTIR of PROBENECID:
Micromeritic properties:
The properties like compressibility index, angle of repose and Hauser ratio were calculated.
Fig 9: Tapped densities from trial T1-T5 Fig 8: bulk densities from trial T1-T5
Practical yield:
Table 6: Percentage yield of all trials T1-T10
Trials F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
Theoretical Weight 460 435 410 385 360 475 465 455 445 435
Practical Weight 480 447 421 411 381 494 488 472 482 452
Percent Yield 95.83 97.31 97.38 93.67 94.48 96.15 95.28 96.39 92.32 96.23
Content uniformity:
Fig 16: theoretical content uniformity in practical yield of microspheres form trial T1-T10
Content uniformity:
Table 11: percent yield and content uniformity form optimized trial T10
theoretical 50% practical Content Content Percent
Theoretical Practical Percent content yield uniformity in uniformity in 462 of drug
TRIAL
weight yield yield uniformity microspheres- 231 Mg. Mg. in 462
practical yield Mg. microspheres microspheres Mg.
F10 435 462 94.15 42.78 231 19.13 38.26 Mg. 95.65%
In-vitro drug release studies:
Fig 20: Graphical representation of probenced release from optimized trial T10
Table 13: Drug release rate kinetic parameters for optimized trial T10
FIRST ORDER HIGUCHIS ODEL KORESMEYER PEPPAS PLOT
ZERO ORDER
% drug sq. mean % drug log log cumulative %
time time log 100-Q
undissolved time dissolved time drug dissolved
0 100 0 2 0 0 0 0
30 96.57 30 1.98 5.48 3.43 1.48 0.53
60 92.45 60 1.97 7.75 7.55 1.78 0.88
120 88.01 120 1.94 10.95 11.99 2.08 1.08
180 86.94 180 1.94 13.42 13.06 2.26 1.12
240 85.28 240 1.93 15.49 14.72 2.38 1.17
300 84.85 300 1.93 17.32 15.15 2.48 1.18
360 84.32 360 1.93 18.97 15.68 2.56 1.20
420 83.9 420 1.92 20.49 16.10 2.62 1.21
DISCUSSION: ACKNOWLEDGEMENT:
Based on the review of literature and FTIR We authors of the present research work Dr P
compatibility studies API, sodium alginate and SHASHIDHAR, MS RABIA FATIMA, express
Methocel K100 was taken for formulation of sincerer gratitude to our founder and chief promoter
PROBENCED MICBEADS/MICROSPHERES. late Sri Dr. Mohammed Vizarat Rasool Khan and
Using sodium alginate formulation trials from T1 to chairman Mr. Mohammed Shah-Alam for providing
T5 were performed, from trial T1 to T5 the percent good infracture and facilities for undergoing and
practical yield, content uniformity are given in table completing the present research work and we also
no 6 and similarly using Methocel K100 formulation thank Dr. M Sunitha Principal, for her continuous
trials from T6-T10 were carried out by varying the support and in-time ideas for attaining the objective
concentration of polymers based on the drug of present research work.
entrapment and drug release studies, and the results
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