FORMULATION AND INVITRO EVALUATION OF LURASIDONE PULSATILE DRUG DELIVERY

Abstract

The development of site-specific, pulsatile drug delivery systems (DDS) aims to optimize therapeutic efficacy and minimize side effects by ensuring drug release at a predetermined time and site within the gastrointestinal tract. This study explores the formulation and evaluation of an oral pulsatile drug delivery system utilizing Lurasidone, an atypical antipsychotic agent, as a model drug. Lurasidone is primarily used in the treatment of schizophrenia and bipolar disorder, conditions requiring precise and timely drug release to align with the body's circadian rhythms and symptom fluctuations. The proposed system integrates time-controlled release mechanisms to target drug release at specific segments of the gastrointestinal tract, particularly the colon. This is achieved through the use of a combination of pH-sensitive polymers, enzymatically degradable materials, and chronotherapeutic approaches. The formulation involves a core tablet containing Lurasidone, coated with a series of layers designed to delay drug release until reaching the desired site of action. In vitro dissolution studies and in vivo pharmacokinetic evaluations are conducted to assess the lag time, release profile, and bioavailability of Lurasidone from the pulsatile DDS. The results demonstrate a significant improvement in the synchronization of drug release with the targeted site, achieving a pulsatile release pattern conducive to the management of psychiatric conditions. An insoluble hard gelatin capsule body, filled with a powder blend, and sealed with a hydrogel plug make up the fundamental design. The powder mix including talc, MCC, crospovidone, Lycoat, and Ludiflash as disintegrants, and Lurasidone as the medication was made and tested for flow characteristics using FTIR analysis. The F12 powder mix formulation was chosen for additional pulsatile capsule production based on the findings obtained. To maintain an appropriate lag duration, a hydrogel plug was produced in a 1:1, 1:2, and 2:1 ratio combining hydrophobic polymers such lactose with hydrophilic polymers like HPMC. It was discovered that the percentage of polymers utilized influenced the drug release. The produced formulations were assessed for In vitro release studies, drug content, and weight variance. Lurasidone was found to be released from the pulsincap after a predefined lag time of six hours, according to in vitro release experiments of the pulsatile device. FTIR measurements verified that there was no interaction between the medication and polymers. It was discovered that PC5F12 was an optimal formulation based on conducted in vitro investigations.