Development and Analysis of Long Acting Depot Formulation for Pharmaceutical Use

Abstract

A new dissolution control type of depot formulation for iloperidone was prepared and evaluated newlinefor in vivo release study in animals. Pamoic acid was used as a counter acid to develop an acid newlineaddition salt of Iloperidone (ILO). The salt was separated using antisolvent precipitation newlinetechnique. For estimation of ILO in salt and rabbit plasma, HPLC method was developed and newlinevalidated which was further used for measurement of drug content and solubility studies of newlinedeveloped salt as well as in pharmacokinetic studies. The developed salt was evaluated with newlinerespect to, particle size and residual solvent with the use of different analytical techniques (viz. newlineHPLC, GC, DSC, Mass spectrometry and XRPD) and process reproducibility. The solubility of newlinesalt formulation was 10 times lesser than ILO. The toxicity study of formulation was carried out newlinein mice for 28 days which revealed that acute toxicity value of LD50 was observed 125 mg/kg. newlineThe LD50 in mice was 25 times higher than the current dose of formulations. The developed ILO newlinepamoate salt and ILO API was injected intramuscularly in rabbits for pharmacokinetic study. newlineAPI could maintain the drug plasma concentration above 4 ng/ml for 27 days in the rabbit model, newlinewhile salt was able to maintain the drug plasma concentration up to 40 days. Based on newlinepharmacokinetic and toxicity study of ILO pamoate salt in animal models, it can be concluded newlinethat, the developed salt is safe and can give control release of ILO. The developed formulation newlinecan be clinically tested in humans for further proving their safety and efficacy. newline