Development of the novel formulations of perospirone for the treatment of schizophrenia.

Abstract

Schizophrenia is a severe mental illness. Its clinical features include positive symptoms (hallucinations, delusions, thought disorders), negative symptoms (avolition, anhedonia, poverty of thought, social withdrawal), and cognitive dysfunction. A large number of antipsychotic drugs with traditional dosage forms are available to mitigate the symptoms of schizophrenia but the duration of action is commonly short, often requiring frequent administration. The perospirone hydrochloride hydrate (PER), as a second-generation antipsychotic drug, shows therapeutic effects on both positive and negative symptoms of schizophrenia, with less impact on cognitive function. However, it suffers from a short half-life, fluctuating blood concentration, instability in the circulating leading to peak-trough fluctuations, and poor patient compliance due to the required frequent administration. Based on the hydrophilic matrix, we developed novel formulations of PER, including the extended-release and the controlled-release tablets of PER. The resulting formulations delayed the drug release and prolonged the persistence of PER, leading to an extended half-life and reduced fluctuations in blood concentration with stable therapeutic levels and an improved absorption with higher bioavailability, thus reducing dosing frequency. These oral extended-release and controlled-release tablets promise to alleviate patients' medication discomfort and provide long-term sustained drug release. They would provide a platform with broad prospects for the clinical treatment of schizophrenia.