Stability Indicating Liquid Chromatographic Method for Estimation of Trihexyphenidyl Hydrochloride and Risperidone in Tablet Formulation: Development and Validation Consideration
This paper describes validated reverse phase high-performance liquid chromatographic (RP-HPLC) method for simultaneous estimation of trihexyphenidyl hydrochloride (THP) and risperidone (RSP) in the pure powder form and in combined tablet dosage form. The HPLC separation was achieved on a core shell C18 (100？mm length？×？4.6？mm, 2.6？μm particle size) using methanol : ammonium acetate buffer 1% (85？:？15 v/v; pH-6.5) as mobile phase and delivered at flow rate of 0.8？mL/min. The calibration plot showed good linear relationship with r2 = 0.997 ± 0.001 for THP and r2 = 0.998 ± 0.001 for RSP in concentration range of 50–175？μg/mL and 50–175？μg/mL, respectively. LOD and LOQ were found to be 0.40 and 1.29？μg/mL for THP and 1.24 and 3.92？μg/mL for RSP. Assay of THP and RSP was found to be 100.16？±？0.03% and 99.83？±？0.02%, respectively. THP and RSP were subjected to different stress conditions (acidic, basic, oxidative, thermal, and photolytic degradation). The degraded product peaks were well resolved from the pure drug peak. The method was successfully validated as per the ICH guidelines. The developed RP-HPLC method was successfully applied for the estimation of THP and RSP in tablet dosage form. 1. Introduction Trihexyphenidyl hydrochloride, chemically known as 1-cyclohexyl-1-phenyl-3-(piperidin-1-yl)propan-1-ol, is one of the centrally acting muscarinic antagonists used for the treatment of parkinsonian disorders and drug-induced extrapyramidal movement disorders and as an antispasmodic. Risperidone (RSP), chemically known as 3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl) piperidin-1-yl]ethyl}-2-methyl-4H, 6H, 7H, 8H, 9H-pyrido [ -a] pyrimidin-4-one, is benzisoxazole derivative and an atypical antipsychotic drug with high affinity for 5-hydrotryptamine (5-HT) and dopamine D2 receptors. It is used primarily in the management of schizophrenia, inappropriate behaviour in severe dementia, and manic episodes associated with bipolar I disorder. RSP is effective in treating the positive and negative symptoms of schizophrenia owing to its affinity for its “loose” binding affinity for dopamine D2 receptors and additional 5-HT antagonism compared to first generation antipsychotics, which are strong, nonspecific dopamine D2 receptor antagonists. Both trihexyphenidyl hydrochloride (THP) and RSP are official in pharmacopoeia. A literature survey revealed that high-performance liquid chromatography (HPLC) for determination of THP and RSP in tablet [1–3] was reported. Further, HPLC method for estimation of RSP in plasma [4], bulk drug and pharmaceutical formulation [5], tablet
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