Formulation development and optimization of prasugrel final dosage form by direct compression method

Abstract

Background:
Prasugrel is a member of thienopyridine class of ADP receptors that reduce the aggregation (“Clumping”) of platelets by irreversibly binding to P2Y12 receptors.

Objective:
The aim of this study is to develop new formulation of Prasugrel tablets by direct compression method which is simple and cost-effective manufacturing technique.

Methods:
To obtain the best optimized product by applied central composite rotatable design (CCRD) software, nine different formulations were developed. Magnesium stearate and croscarmellose sodium were taken as independent variables. Blends were examined for various evaluating parameters like apparent bulk and tapped density, compressibility index, angle of repose and lose on drying. Newly developed compressed tablets were then evaluated using pharmacopeial and non-pharmacopeial tests for physical and chemical characteristics of core tablets i.e., hardness, weight variation test, friability (%), disintegration test (min) whereas coated tablets were evaluated for weight variation, Assay and dissolution. Three different dissolution media i.e. 0.1N HCl (pH 1.2), phosphate buffer pH 4.5 and pH 6.8 were used for calculating the percentage release of Prasugrel and their release pattern was compared with innovator brand by using the model independent methods like similarity (f2), dissimilarity (f1) and model dependent methods like first order, Hixson Crowell method and Weibull method. Micromeritic properties of powder blends were within acceptable limits of all nine formulations.

Results:
All the physio chemical tests found satisfactory and comparable with reference product. The comparative dissolution profile results revealed that Trial-05 showed maximum similarity i.e., 71.16, 72.59 and 68.49 at three different pH dissolution media. Dissimilarity factor was also comparable in Trial 5 i.e., 2.66, 4.63 and 3.95 at 0.1HCl, buffer pH 4.5 and 6.8 respectively. Model dependent approaches showed the maximum r 2 values of Trial 5 i.e., greater than 0.900 at all three reported pH. Results also explained that model dependent comparison is best choice as compared to model impendent approaches.

Conclusion:
New formulation of Prasugrel tablets final dosage form was developed and optimized and evaluated based on physiochemical parameters which were found satisfactory. Comparative dissolution profile results revealed that drug is comparable with reference product in term of efficacy.
Highlights:
The developed formulation offers various advantages over innovator brand in terms of patient compliance as well as in terms of cost effectiveness and easy to manufacture.

Materials, Standards, Reagents and Chemicals

a) Microcrystalline cellulose PH-102 – (FMC Corporation, USA).

b) Croscarmellose sodium – (FMC Corporation, USA).

c) Magnesium stearate – (Dow chemicals, USA).

d) HPMC (E-5) – (FMC Corporation, USA).

e) Titanium dioxide – (FMC Corporation, USA).

f) Polyethylene glycol – (FMC Corporation, USA).

g) Instacoat blue – (FMC Corporation, USA).

h) Prasugrel – API and Standard – HEC pharma, Shaoguan city, China

i) Acetonitrile – HPLC grade (Fisher scientific, USA).

j) Potassium dihydrogen phosphate – Analytical grade (Merck, Germany).

k) Sodium citrate – Analytical grade (Merck, Germany).

l) Sodium dihydrogen phosphate – Analytical grade (Merck, Germany).

m) Hydrochloric acid – Analytical grade (Merck, Germany).

n) Water – Purified in-house using the Milli-Q integral 3 system.

o) Sample – Obtained from Department of Pharmacy, University of Karachi.

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Uzma Asif; Asif Khan, FORMULATION DEVELOPMENT AND OPTIMIZATION OF PRASUGREL FINAL DOSAGE FORM BY DIRECT COMPRESSION METHOD,Journal of Tianjin University Science and Technology, 56,
DOI: 10.17605/OSF.IO/6DZVE