Controlled Release Matrix Formulation of Paliperidone in Concurrence with Regulatory Requirements

Authors

  • DEEPAK MAHESHWARI Department of Pharmaceutics, School of Pharmacy, RK University, Rajkot, Gujarat, India
  • Chetan Detroja Department of Pharmaceutics, School of Pharmacy, RK University, Rajkot, Gujarat, India

Abstract

Paliperidone is the 9-hydroxy metabolite (9-hydroxy) of risperidone and is a psychotropic drug of the atypical antipsychotic family. Paliperidone has the racemates (+)- and (-)-paliperidone. It is a dopamine D2 antagonist with serotonergic 5-HT2A antagonistic action that acts centrally. ALZA OROS® osmotic medication release technology is used to create Invega ER tablets. It is a tri-layer longitudinally compressed tablet based on a sophisticated osmotic delivery method that is meant to administer the paliperidone in a defined way over 24 hours. This research aims to create a generic controlled-release single-layer matrix tablet of paliperidone. Different combinations of Polyox and hypromellose in the core were used, followed by coating, to assist/build a stable and strong formulation. All strengths have similar in-vitro dissolution profiles. Freeze formulation was assessed for nitrosamine risk assessment as well as challenge for alcohol dose dumping study. Paliperidone is a basic compound with a pKa1 of 8.2 (piperidine moiety) and a pKa2 of 2.6 (pyrimidine moiety). As a result, a substantial portion of the molecule is ionized at physiological pH. It is relatively insoluble in water (0.003 g/100 mL water at pH 7.4). The solubility decreases at higher pH (0.001 g/100 mL at pH 12.9) and significantly increases at lower pH (3 g/100 mL at pH 5.3). The partition coefficient octanol/water (log P) is 2.39. Hence, discriminating media was identified as pH 2.75 buffer. The Higuchi model was used for expressing the in-vitro release profile through matrix composition. Formulation withstands 0–40% alcoholic conditions under in-vitro release tests. It is easy to formulate, stable and cost-effective. The manufacturing process involves dry blending followed by compression and coating so there will be the least chemical interaction of an active substance with other excipients. Hence, there is a negligible possibility to generate nitrosamine impurity in the formulation. The formulation is classified as rugged against dose dumping.

Keywords:

Paliperidone, osmotic, Polyox, Regulatory, Biowaiver, Discriminating, Nitrosamine, Alcohol dose dumping

DOI

https://doi.org/10.25004/IJPSDR.2023.150405

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Published

15-07-2023
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How to Cite

“Controlled Release Matrix Formulation of Paliperidone in Concurrence With Regulatory Requirements”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 15, no. 4, July 2023, pp. 426-31, https://doi.org/10.25004/IJPSDR.2023.150405.

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Research Article

How to Cite

“Controlled Release Matrix Formulation of Paliperidone in Concurrence With Regulatory Requirements”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 15, no. 4, July 2023, pp. 426-31, https://doi.org/10.25004/IJPSDR.2023.150405.

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