Formulation and Evaluation of Extended Release Trihexyphenidyl Hydrochloride Hard Gelatin Capsules

DOI:

https://doi.org/10.37285/ijpsn.2011.4.1.8

Authors

  • Madhusudan Rao Y
  • Vinay Kumar K
  • Jagan Mohan S
  • Kiran Kumar V

Abstract

This work aims at investigating different types and levels of hydrophilic high molecular weight matrix agents, (including HPMC K15M, Metalose-60 SH, Metalose-65 SH and Metalose-90SH-SR), hydrophobic diluent (Talc) and formulation methods (Non-aqueous granulation and direct filling by simple mere mixture) in an attempt to formulate hard gelatin extended release matrix capsules containing Trihexyphenidyl HCl (Benzhexol). The drug release from all the extended release matrix capsules show polymer as well as talc concentration dependent retardation affect. The Metalose 90SH-SR concentration was optimized to approximately 27% w/w of total capsule net content weight. The hydrophobic diluent’s talc concentration was optimized and the useful concentration was approximately 17.45% w/w of the total net capsule content weight. The lactose concentration was also optimized and the effective concentration was found to be approximately 48.36% w/w. The prepared hard gelatin extended release capsules were evaluated for weight variation, Average net content, locked length, content uniformity, assay (drug content) and in-vitro drug release studies. From the in-vitro release studies of the prepared formulations, one formula was optimized from each method. All the formulations showed linear release profiles and extended the release of trihexyphenidyl HCl (Benzhexol) over 10 –12 h. The release profiles of extended release matrix capsules of trihexyphenidyl HCl (THP HCl) from the selected formulations were close to zero order and follow diffusion dependent release. The prepared extended release matrix capsules of trihexyphenidyl HCl (Benzhexol) produced from the optimized formulations ‘NAG-M90SH-SR-5 and DB M90SH-SR-4’ complied with the USP XXVII specifications. The difference factor (f1) and similarity factor (f2) was calculated for all these formulations and found to the below 15 and above 50. Irrespective of the formulation method type and its procedure, the prepared hydrophilic extended release matrix capsules showed non-Fickian anomalous transport (coupled diffusion in the hydrated matrix and polymer relaxation) as the values of release exponent (n) are in between 0.50 and 0.89. Finally it was clear that it is possible to design a formulation with any of the above two methods giving the desired drug release profile suggesting that nonaqueous granulation, Direct filling were good methods for preparing extended release matrix capsules of trihexyphenidyl HCl (Benzhexol).

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Keywords:

Trihexyphenidyl HCl (THP HCl, Benzhexol), HPMC K4M, Metalose-60 SH, Metalose-90SH-SR, Metalose-65 SH, Talc, Extended Release Capsules

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Published

2011-05-31

How to Cite

1.
Y MR, K VK, S JM, V KK. Formulation and Evaluation of Extended Release Trihexyphenidyl Hydrochloride Hard Gelatin Capsules. Scopus Indexed [Internet]. 2011 May 31 [cited 2024 Jun. 20];4(1):1359-67. Available from: http://www.ijpsnonline.com/index.php/ijpsn/article/view/413

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Section

Research Articles

References

Alderman, D.A. (1984) A review of cellulose ethers in hydrophilic matrices for oral controlled release dosage forms. Int J Pharm Technol Prod Manuf. 5: 1Y9.

Ashwin Patel, Alankar Shrivastava, Anurekha Jain and GK singh. (2009) Method development and validation for estimating of trihexyphenidyl hydrochloride in tablet dosage form.

Bala Ramesh Chary, R., and Madhusudan Rao, Y. (2000) “Formulation and evaluation of methocel K15M bioadhesive matrix tablets.” Drug Development and Industrial Pharmacy, 26(8).

Erni, W., and Held, K. (1987) The hydrodynamically balanced system: a novel principle of controlled drug release. Eur Neurol. 27:21Y27.

Kamal A. Hadidi. (2004) Development of screening method for most commonly abused anticholinergic drugs in Jordan; trihexyphenidyl, procyclidine and biperidin.

Korsmeyer, R.W., Gurny, R., Doelker, E.,Buri, P., and Peppas, N.A. (1983) Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm.15: 25Y35.

Krishna Veni, Jayasagar, G. and Madhusudan Rao, Y. (2001) “Formulation and evaluation of diclofenac sodium, usinghydrophilic matrices.” Drug Development and Industrial Pharmacy, 27(8): 161-168.

Moore JW, Flanner HH. 1996. Mathematical com- parison of curves with an emphasis on in-vitro dissolution profiles. Pharm Technol 20:64-74.

Peppas, N. A. (1985) Analysis of Fickian and Non-Fickian Drug Release from polymers. Pharm. Acta. Helv. 60, 110-111.

Qiu, Y., Zhang, G., (2000) Research and Development Aspects of Oral Controlled-Release Dosage Forms in Handbook of Pharmaceutical Controlled Release Technology (Wise, D. L. Edt), Marcel Dekker Inc.

Raghuram, R.K., Srinivas, M., and Srinivas, R. (2003) Once-daily sustainedrelease matrix tablets of nicorandil: formulation and in-vitro evaluation.AAPS PharmSciTech [serial online]. 4:E61.

Reza, M.S., Abdul Quadir, M., and Haider, S.S. (2003) Comparative evaluation of plastic, hydrophobic and hydrophilic polymers as matrices for controlled-release drug delivery. J Pharm Pharm Sci.6: 282Y291.

Ritger, P.L., and Peppas, N.A. (1987) A simple equation for description of solute release, II: Fickian and anomalous release from swellable devices. J Control Release.5:37Y42.

USP. Metalose SR (Hypermellose), Sustained release agent for matrix systems.