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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.

Background: Targeting anti-tubercular therapeutics to alveolar macrophages using microparticles technology mainly focuses on increasing local concentrations of therapeutics and potentially reducing the frequency of dosing requirements. Rifampicin (RIF), Ofloxacin (OFX) and Ethambutol (ETH) combination show synergism. Objective: In light of the above facts, the focus of the present study was to develop and characterize novel Dry powder Inhaler formulation incorporating novel drug combination as a pulmonary delivery for the effective eradication of Tuberculosis. Method: Biodegradable microparticles containing RIF, OFX and ETH were prepared by a spray drying technique using PLGA polymer through the critical process as well as polymer attributes were screened and optimized using 23 factorial design. The identified critical process parameters (CPP’s) viz. Inlet temperature, Aspiration rate, and feed rate were selected as independent variables while percentage yield, percentage entrapment efficiency, and particle size were selected as a response. The formulated microparticles were evaluated for particle size, drug-polymer compatibility study, aerodynamic behavior, morphology, particle size distribution, crystallinity, residual solvent content, in-vitro drug release study, and stability study. Results: By choosing the optimum spray drying conditions maximum yield of 73%, entrapment efficiency of 86% and particle size of 1.4 μm was attained of the optimized batch. Thus the results revealed that spherical microparticles are suitable for inhalation and sustained release for 12 h. Conclusion: The successful formulation and evaluation of dry powder could be used as an enhanced therapeutic alternative of the standard oral anti-tubercular regimen, rescuing oral dosing, shortening drug regimen and limiting toxicity. This will ultimately improve patient compliance and diminish the prevalence of MDR resistance.

The major oral solid medicines are sold in blister and strips packaging, which are packaged in a carton box. Children, who manage to open such boxes, while unsupervised, are in great danger of being poisoned by swallowing the contents. A CRP usually requires a special trick to open it. The aim was to design and validate the performance of innovative CRP system with unique features. Materials used were the plastic grade, click lock system, and blister pack. The test conducted on test panels of 100 healthy children between 42 and 51 months were asked to open a pack. Each panel divided into 3 groups, viz. 30 children of 42–44 months, 40 children 45–48 months, and 30 children 49–51 months. The panel of 100 healthy adults divided into 3 groups, viz. 25 adults 18–40 years, 25 adults 40–59 years, and 50 adults 60–70 years. Results shown only 6% of children succeeded to open CRP, while 94% failed to open CRP within 5 min. In the case of adults, 96% succeeded to open CRP without imposing any difficulties. There was a successful development of a prototype of CRP, which can used for the packaging of pharmaceutical products. CRP deprived children to have access of medicated packaging system, which resulted in devoid of any poisonous effect to the children.

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.

The present study was designed to formulate and develop fast disintegrating pellets of poorly soluble model drug (cilostazol) by reducing the proportion of micro-crystalline cellulose with pre-gelatinized starch (PGS), lactose and chitosan. The bioavailability enhancement of a model drug was achieved by preparing inclusion complex with Captisol® (Sulfobutyl Ether β cyclodextrin - SBE-β-CD). Extrusion-spheronization technique was used to formulate pellets. Placket-Burman design was used for the initial screening of most significant factors such as screen size (mm), ratio of micro crystalline cellulose: PGS + lactose + chitosan and % of HPMC which affects pellet properties. The inclusion complex of drug and Captisol

Objective: The focus of this study was to develop in situ injectable implants of Lornoxicam which could provide sustained drug release. Methods: Biodegradable in situ injectable implants were prepared by polymer precipitation method using polylactide-co-glycolide (PLGA). An optimized formulation was obtained on the basis of drug entrapment efficiency, gelling behavior and in vitro drug release. The compatibility of the formulation ingredients were tested by Fourier transform infrared (FT-IR) spectroscopy, and differential scanning colorimetry (DSC). SEM study was performed to characterize in vivo behavior of in situ implant. Pharmacokinetic study and in vivo gelling study of the optimized formulation were performed on Sprague-Dawley rats. Stability testing of optimized formulation was also performed. Results: The drug entrapment efficiency increased and burst release decreased with an increase in the polymer concentration. Sustained drug release was obtained up to five days. SEM photomicrographs indicated uniform gel formation. Chemical interaction between the components of the formulation was not observed by FT-IR and DSC study. Pharmacokinetic studies of the optimized formulation revealed that the maximum plasma concentration (Cmax), time to achieve Cmax (Tmax) and area under plasma concentration curve (AUC) were significantly higher than the marketed intramuscular injection of lornoxicam. Stability study of optimized batch showed no change in physical and chemical characteristics. Conclusion: Lornoxicam can be successfully formulated as in situ injectable implant that provides long-term management of inflammatory disorders with improved patient compliance.

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.

The present research work was undertaken to formulate modified release tablets of lornoxicam using Compritol 888 ATO as a lipid matrixing agent and to evaluate the tablets for dissolution in hydro-alcoholic dissolution media to meet the requirement of regulators. The dissolution study was also conducted in aqueous medium containing alcohol and hydroxylpropyl methylcellulose to mimic the viscosity and pH after food and alcohol intake. The tablets were prepared by direct compression by adopting the concept of design of experiments and evaluated mainly for dissolution studies in aqueous dissolution media containing 10, 25 and 40% ethyl alcohol. The formulated tablets satisfied the USP requirements of drug release at 2, 6 and 10 hr. The drug release was insignificantly altered when the dissolution study was conducted in media containing increasing amount of alcohol probably due to higher solubility of the drug in alcohol. The drug release was suppressed when HPMC was used in the dissolution media. This may be due to rise in viscosity of the dissolution media. Dose dumping was not noticed under the experimental conditions.

The conventional liquid ophthalmic delivery systems exhibit short pre-corneal residence time and the relative impermeability to the cornea which leads to poor ocular bioavailability.The aim of this study was to apply quality by design (QbD) for development of dexamethasone sodium phosphate (DSP) and tobramycin sulfate (TS)-loaded thermoresponsive ophthalmic in situ gel containing Poloxamer 407 and hydroxyl propyl methyl cellulose (HPMC) K4M for prolonging the pre-corneal residence time, ocular bioavability and decreases the frequency of administration of dosage form. The material attributes and the critical quality attributes (CQA) of the in situ gel were identified. Central composite design (CCD) was adopted to optimize the formulation.The ophthalmic in situ forming gels were prepared by cold method. Materials attributes were the amount of Poloxamer 407 and HPMC and CQA identified were Gel strength, mucoadhesive index, gelation temperature and % of drug release of both drug.Optimized batch (F*) containing 16.75% poloxamer 407 and 0.54% HPMC K4M were exhibited all results in acceptable limits. Compared with the marketed formulation, optimized in situ gel showed delayed Tmax, improved Cmax and AUC in rabbit aqueous humor, suggesting the sustained drug release and better corneal penetration and absorption.According to the study, it could be concluded that DSP and TS would be successfully formulated as in situ gelling mucoadhesive system for the treatment of steroid responsive eye infections with the properties of sustained drug release, prolonged ocular retention and improved corneal penetration.

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.

Withaferin A, a steroidal lactone which is present in dry root extract of Withania somnifera (WSE), is reported to possess numerous pharmacological activities and shows poor aqueous solubility. The purpose of this study is to enhance the dissolution rate and oral bioavailability of WSE by incorporating it in self nano emulsifying drug delivery system (SNEDDS). Capmul MCM-based SNEDDS formulation with Tween 20 as surfactant and ethanol as co surfactant was developed for oral delivery of withaferin A. Optimised SNEDDS was evaluated for its self-emulsification time and viscosity, droplet size. The optimised SNEDDS formulation containing withaferin A, Capmul MCM(12.4%), Tween 20 (58.2%) and ethanol (29%), and showed higher in vitro drug release as compared to pure WSE. These results demonstrate the potential use of SNEDDS for improving the oral bioavailability of poor water soluble compounds such as withaferin A.

Ratio derivative spectrophotometric method has been developed for the simultaneous determination of artemisinin and curcumin. The overlapping spectra of both drugs were resolved by making use of the first-derivative of the ratios of their direct absorption spectra. The derivative ratio absorbances of artemisinin and curcumin were measured at λmax 293.17 and λmax 457.0 nm, respectively, for their quantification. Artemisinin and curcumin were determined in the concentration range of 2-10 μg/mL and 1-5 μg/mL, respectively. The method was validated as per the ICH guidelines and accuracy, precision were found to be within acceptable limit. The limits of detection and quantitation were found to be 0.003299 and 0.009997 μg/mL, respectively for artemisinin and 0.006743 and 0.020434 μg/mL, respectively for curcumin. The proposed ratio first derivative spectrophotometric method is novel, rapid, simple, sensitive, accurate, precise and successfully applicable for simultaneous estimation of artemisinin and curcumin in parentral dosage form.