Aslam, N. | Search bioRxiv

bioRxiv2022

Design And Optimization Studies Of Tablet In Tablet Formulation Of Diclofenac And Misoprostol: Application Of Response Surface Methodolgy And Compressional Behaviour Strategy

The present study was aimed to develop compression coated tablets of diclofenac sodium (75mg) in the inner core and misoprostol (200 mg) as the outer shell for the effective treatment of rheumatoid arthritis as this dosing frequency is not available in the market yet. Diclofenac sodium inner tablet was manufactured by wet granulation and its enteric coating was applied by Eudragit L 100-55, Isopropyl Alcohol and Opadry II Blue 85 F205034. While immediate-release misoprostol outer shell was also manufactured by wet granulation and coated by Opadry white and Polyethylene glycol 6000. Design of experiment(R) software was used for formulation design and optimization. Quality attributes such as tablet weight, hardness, disintegration time, percent drug dissolution and assay were performed as per official methods and satisfactory results were reported. Physical and chemical stability of selected formulations was evaluated following the ICH guidelines for accelerated stability testing. The compressional analysis of optimized formulation was performed to check the optimum compression pressure to obtain a stable formulation. Based on satisfactory quality attributes; formulation DF9MF7 was successfully developed as compression coated tablet with calculated shelf life of 4.8years. Compression coated tablets comprising of enteric coated diclofenac sodium as inner core and misoprostol as outer shell were successfully developed by wet granulation.

pharmacology and toxicology↗

bioRxiv2019

A systems biology-based molecular model of the protein kinase C life cycle

Protein kinase C (PKC) enzymes are a family of kinases that mediate signal transduction originating at the cell surface. Most cell membranes can contain functional PKC enzymes. Aberrations in the PKC life cycle may result cellular damage and dysfunction. For example, some cancerous cells exhibit alterations in PKC activity. Here, we use a systems biology approach to describe a molecular model of the PKC life cycle. Understanding the PKC life cycle is necessary to identify new anticancer drug targets. The PKC life cycle is composed of three key regulatory processes: maturation, activation and termination. These processes precisely control PKC enzyme levels. This model describes the fate of PKC during de novo synthesis and PKCs lipid-mediated activation cycle. We utilize a systems biology approach to show the PKC life cycle is controlled by multiple phosphorylation and dephosphorylation events. PKC processing events can be divided into two types: maturation via processing of newly synthesized enzyme and secondary messenger-dependent activation of dormant, but catalytically-competent enzyme. Newly synthesized PKC enzyme is constitutively processed through three ordered phosphorylations and stored in the cytosol as a stable, signaling-competent inactive and autoinhibited molecule. Upon extracellular stimulation, diacylglycerol (DAG) and calcium ion (Ca+2) generated at the membrane bind PKC. PKC then undergoes cytosol-to-membrane translocation and subsequent activation. Our model shows that, once activated, PKC is prone to dephosphorylation and subsequent degradation. This model also describes the role of HSP70 in stabilization and re-phosphorylation of dephosphorylated PKC, replenishing the PKC pool. Our model shows how the PKC pool responds to different intensities of extracellular stimuli? We show that blocking PHLPP dephosphorylation replenishes the PKC pool in a dose-dependent manner. This model provides a comprehensive understanding of PKC life cycle regulation.

systems biology↗