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Diabetic wounds (DWs) are the major end-stage manifestation encountered in diabetic patients. The two major pathways involved in the pathogenesis of DW are impaired angiogenesis and unnecessary NETosis, which are regulated by a common enzyme called protein kinase C (PKC)-βII. PKC-βII is a conventional isoform of PKC family that can be activated by calcium and diacylglycerol. PKC-βII possesses a specific expression profile and plays a distinct role in various cellular and molecular functions. The pathogenic role of PKC-βII and its involvement in the impairment of wound healing suggested that PKC-βII plays a potential role in DW progression. Hence, there is a renewed interest in developing specific inhibitors of PKC-βII. In the present study, receptor-based virtual screening was performed for the identification of potential PKC-βII inhibitors using TimTec, Enamine, Zinc and Specs databases. A total of 595 candidate compounds were evaluated based on absorption, distribution, metabolism, excretion and toxicity, standard precision docking. Further, extra-precision docking and binding free energy calculations were carried out for top-ranked compounds. Based on Glide score and protein-ligand interactions, we have identified compound 1 as a potential inhibitor. Finally, molecular dynamics (MD) simulation was performed for top compound 1 using the Desmond module (Schrödinger suite) to identify the structural stability of the protein-ligand complex. Gratifyingly, MD trajectory analysis demonstrated the stable binding conformation of compound 1 with PKC-βII enzyme. In silico approaches incorporated in this study provide a set of new putative PKC-βII inhibitors which could be potential leads to develop DW therapeutics.

Objectives: The aim of the present investigation was to develop a solid dispersion of itraconazole (ITR) using sacrificial excipients like pregelatinized starch and spray-dried lactose alongside hydroxypropyl methylcellulose and Poloxamer 188, thereby arresting the conversion of the amorphous form of ITR to crystalline form, and to assess the dissolution stability of an amorphous form of the drug during short-term storage. Materials and Methods: ITR-loaded solid dispersions were prepared by kneading. Formulation optimization was achieved by using a 24 full factorial design on the basis of cumulative percent drug released at t30, t60, and t120 min. An artificial neural network (ANN) was also applied as a statistical tool for obtaining better predictive ability and the outcomes of the ANN were compared with that of Design-Expert software. Results: The spectral data revealed no drug–carrier interactions. The P-X-ray diffraction study of the optimized batch showed a decrease in the crystallinity of drug as compared to the untreated drug. The in vitro dissolution studies of the optimized batch showed higher dissolution (92% at 120 min) in comparison to the other formulations. The dissolution stability study was performed at 40°C and 75% relative humidity for 90 days for the optimized formulation. The results of the optimized batch showed insignificant changes in cumulative percentage drug release during storage. Conclusion: Dissolution stability could be attributed to the presence of sacrificial excipients as they tend to absorb moisture during storage and possibly get converted into crystalline form, thereby minimizing the recrystallization of ITR.

Introduction: The Bacopa monnieri is traditional Ayurvedic medicine, and reported for memory-enhancing effects. The Bacoside is poorly soluble, bitter in taste and responsible for the memory enhancement action. Memory enhancer is commonly prescribed for children or elder people. Objective: Poor solubility, patient compliance and bitterness were a major driving force to develop taste masked β-cyclodextrin complex and dispersible tablets. Materials and Methods: The inclusion complex of Bacopa monnieri and β-cyclodextrin was prepared in different molar ratios of Bacopa monnieri by Co-precipitation method. Phase solubility study was conducted to evaluate the effect of β-cyclodextrin on aqueous solubility of Bacoside A. The characterization was determined by Fourier transformation infrared spectroscopy (FTIR),Differential scanning calorimetry (DSC) and X-ray diffraction study (XRD).Crospovidone and croscarmallose sodium were used as super disintigrant.The 32 full factorial design was adopted to investigate the influence of two superdisintegrants on the wetting time and disntegration time of the tablets. Conclusion: The result revels that molar ratio (1:4) of inclusion complex enhance 3-fold solubility. Full factorial design was successfully employed for the optimization of dispersible tablet of B. monnieri . The short-term accelerated stability study confirmed that high stability of B. monnieri in inclusion complex.

Introduction: The aim of burn management and therapy is fast healing and epithelisation to prevent infection. The present study is concerned with the development and characterization of a novel nanaoparticulate system; cubosomes, loaded with silver sulfadiazine (SSD) and Aloe vera for topical treatment of infected burns. Methods: Cubosome dispersions were formulated by an emulsification technique using different concentrations of a lipid phase Glyceryl Monooleate (GMO) and Poloxamer 407. The optimum formulae were incorporated in an aloe vera gel containing carbopol 934, to form cubosomal hydrogels (cubogels). The cubogels were characterized by in vitro release of SSD, rheological properties, pH, bioadhesion, Transmission Electron Microscopy and in-vivo Wound Healing Study. Results: The results show that the different concentration of GMO had significant effect on particle size, % EE and in vitro drug release. From the in-vitro drug release pattern and similarity factor (f 2 ), it was concluded that batch CG3 (15% GMO and 1% P407) exhibited complete and controlled drug release within 12 hour (i.e. 98.25%), better bio adhesion and superior burn healing as compared to the marketed product. Conclusion: The in vivo burns healing study in rats revealed that the prepared optimized cubogel containing SSD and aloe vera has superior burns healing rate than cubogel with only SSD and marketed preparation so, it may be successfully used in the treatment of deep second degree burn.