Formulation and Evaluation of Extended Release Trihexyphenidyl Hydrochloride Hard Gelatin Capsules

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 beapproximately 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 formulationsshowed 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 trihexyphenidylHCl (Benzhexol).