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