STUDY OF DIRECT COMPRESSION METHOD FOR THE PREPARATION OF QUINAPRIL HYDROCHLORIDE TABLETS

  • SHWETHA MARGRET JL Department of Pharmaceutics, RBVRR Women’s College of Pharmacy, Barkatpura, Hyderabad, Telangana, India.
  • MADHAVI BLR Department of Pharmaceutics, Acharya and BM Reddy College of Pharmacy, Bengaluru, Karnataka, India.

Abstract

Objective: Direct compression method is preferable for tablet manufacture. The direct compression method is followed for many formulations but the relevant study is not reported. The present work aims to study the suitability of the direct compression process to prepare tablets of quinapril hydrochloride (QHCl), a low dose drug with a starting dose of 5 mg, indicated in the treatment of hypertension, congestive heart failure, and other conditions.


Methods: QHCl is reported to be unstable in the presence of moisture, heat, and some excipients. The direct compression method was tried instead of a wet granulation technique to prepare the tablets. Initially, drug-excipient compatibility study was carried out. For selected excipients and QHCl preformulation tests were conducted. The stabilizer was employed. Three formulations were tried. The blends were prepared by tumbling and trituration methods. Blend uniformity and precompression parameters were determined. Tablets were directly compressed and evaluated.


Results: Drug-excipient compatibility was studied at 60°C and 40°C with an Relative humidity (RH) of 75% for 4 weeks. It showed discoloration of the pure drug and most of the drug excipient mixtures. Three formulations Q1, Q2, and Q3 were prepared using magnesium oxide (light), magnesium carbonate (light), and Aerosil as stabilizers. Blending was done by trituration and tumbling method for 10 min and 15 min duration for the given batch size. Blend uniformity was determined. Tumbling method for 15 min showed good blending as evident from the percentage coefficient of variation values. The blends had a good flow. Tablet evaluation showed hardness in the range of 2.5–3 kg/cm2 and disintegration time of 1–2 min. Q1 and Q2 passed the friability test. The content uniformity criterion was achieved with an acceptance value <20. In vitro dissolution, Q1 and Q2 were 100% and 98.8%, respectively, in 30 min and followed first-order kinetics. The stability study of Q1 indicated a single peak in the chromatogram corresponding to the drug. Q2 showed spotted discoloration.


Conclusion: The direct compression technique could be employed for the preparation of QHCl tablets. Q1 showed better stability and release characteristics. Q2 and Q3 are considered for further study.

Keywords: Quinapril hydrochloride, Tablets, Direct compression, Blend uniformity, Content uniformity, Stabilizer

References

1. Liberman HA, Lachman L, Schwartz JB. Pharmaceutical Dosage Forms: Tablets. 2nd ed., Vol. 1. USA: Marcel Dekker; 1989.
2. Accupril (Quinapril Hydrochloride) Product Monograph. Canada: Parke Davis and Company Pfizer Inc.; 2017. Available from: https://www.pfizer.ca/sites/default/files/201710/accupril_ pm_200979_e_14mar2017_clean.pdf. [Last accessed on 2019 Nov 21].
3. Stanisz B, Paszun S, Strzyzycka N, Ptaszy?ski E. Influence of humidity and hydroxypropyl cellulose, hydroxypropylmethyl cellulose, glyceryl behenate or magnesium stearate on the degradation kinetics of quinapril hydrochloride in solid phase. Acta Pol Pharm 2010;67:99-102.
4. Stanisz B. The influence of pharmaceutical excipients on quinapril hydrochloride stability. Acta Pol Pharm 2005;62:189-93.
5. Stanisz B. The stability of quinapril hydrochloride--a mixture of amorphous and crystalline forms (QHCl-AC)--in solid phase. Acta Pol Pharm 2003;60:443-9.
6. Guo Y, Byrn SR, Zografi G. Effects of lyophilization on the physical characteristics and chemical stability of amorphous quinapril hydrochloride. Pharm Res 2000;17:930-5.
7. Palem CR, Gannu R, Yamsani SK, Yamsani VV, Yamsani MR. Development of bioadhesive buccal tablets for felodipine and pioglitazone in combined dosage form: In vitro, ex vivo, and in vivo characterization. Drug Deliv 2011;18:344-52.
8. Abed KK, Hussein AA, Ghareeb MM, Abdulrasool AA. Formulation and optimization of orodispersible tablets of diazepam. AAPS PharmSciTech 2010;11:356-61.
9. Fung HL, Yap SK, Rhodes CT. Development of a stable sublingual nitroglycerin tablet II: Formulation and evaluation of tablets containing povidone. J Pharm Sci 1976;65:558-60.
10. Daniel JE, Harris MR, Hokanson GC, Weiss J. Stabilization of Quinapril Using Magnesium Oxide. United States Patent, Patent No. US 6417196B1; 2002. Available from: https://www.patents.google. com/patent/US6417196. [Last accessed on 2019 Apr 18].
11. Harris M, Hokanson G, Murthy K, Reisch R, Frank W. Stabilized pharmaceutical Compositions Containing ACE Inhibitors. European Patent, Patent No. EP0280999; 1993. Available from: https://www.patents.google.com/patent/EP0280999A2/en. [Last accessed on 2019 Apr 18].
12. Murthy KS, Harris MR, Hokanson GC, Reisch RG Jr., Waldman F, Fawzi MB. Stabilized Drug Compositions. United States Patent, Patent No. US4793998A; 1988. Available from: https://www.patents.google. com/patent/US4793998. [Last accessed on 2019 Apr 18].
13. Mali AD, Bathe RS. Development and evaluation of gastroretentive floating tablets of quinapril HCL by direct compression technique. Int J Pharm Pharm Sci 2017;9:35-46.
14. Ranade AN, Ranpise NS, Sanap GS, Kulkarni RR. Development and in vitro evaluation of buccal tablet of quinapril hydrochloride. Indian J Pharm Educ Res 2011;45:364-9.
15. Qui Y, Chen Y, Zhang GZ. Developing Solid Oral Dosage Forms Pharmaceutical Theory and Practice. 1st ed. New York: Elsiever Inc.; 2009. p. 125.
16. Bramhe NN, Kilor VA. Evaluation and optimization of Lepidium sativum seed mucilage as binder in tablet formulation. Int J Pharm Pharm Sci 2014;6:285-91.
17. Uniformity of Dosage Units, the United States Pharmacopeia: USP 29: The National Formulary NF, United States Pharmacopeial Convention; 2006. Available from: http://www.ftp.uspbpep.com/v29240/ usp29nf24s0_c905h.html.
18. Deveswaram R, Bharath S, Concepts and techniques of pharmaceutical powder mixing process: A current update. Res J Pharm Technol 2009;2:245-9.
Statistics
258 Views | 112 Downloads
Citatons
How to Cite
SHWETHA MARGRET JL, and MADHAVI BLR. “STUDY OF DIRECT COMPRESSION METHOD FOR THE PREPARATION OF QUINAPRIL HYDROCHLORIDE TABLETS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 13, no. 1, Nov. 2019, pp. 202-11, doi:10.22159/ajpcr.2020.v13i1.34005.
Section
Original Article(s)