Design, optimization, and characterization of an in-situ pore-forming system for controlled delivery of paliperidone

Abstract

The purpose of the current investigation was to develop a pharmaceutical equivalent osmotic drug delivery formulation of Paliperidone (PLD) in the form of controlled porosity osmotic pump tablets (CPOT) in order to keep the drug's steady state concentration in the body. This helps to achieve the greatest therapeutic benefit with the fewest side effects. For the purpose of identifying various formulation attributes, preliminary trials were conducted. Taguchi design was used to study the influence of seven input factors namely drug to polymer ratio, polymer 1(HPMC K100 M) to polymer 2 (HPMC K15 ​M), drug to total osmogens, coating level, amount of pore former, concentration of ethyl cellulose and amount of plasticizer on dependent variable similarity factor (f2). Utilizing the Minitab 17, data analysis was done. The similarity factor (f2) was computed using the osmotic tablet reference product INVEGA®. The findings demonstrate that each of the seven independent variables significantly affects the similarity factor. For optimized batch, both core and coated tablets showed acceptable pharmaco-technical parameters. The release profile of the optimized batch tablets was found to be similar to that of reference product with good zero-order release pattern. Drug release was observed through the channels formed by in-situ pores on tablet surface performed using SEM. From the results it can be concluded that prepared CPOT of PLD was found pharmaceutical equivalent with commercial product which is cost effective and fully compliance with cGMP.

Keywords

• Controlled release
• pH-independent release
• Similarity factor
• Pharmaceutical equivalent
• Reference product