FORMULATION OF IMMEDIATE RELEASE (IR) ATORVASTATIN CALCIUM PELLETS AND SUSTAINED RELEASE (SR) GLIBENCLAMIDE FOR FIXED-DOSE COMBINATION DOSAGE FORM

Objective: The objective of the present research was to develop fixed-dose combinations for the treatment of dyslipidemia, associated with type-II diabetes mellitus for improvement of glucose tolerance.Methods: Multiple unit pellet systems (MUPSs) consisting immediate release atorvastatin calcium pellets and sustained release glibenclamide were formulated by spheronization technique. The characterization of formulated pellets was done by Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC) studies, and formulated pellets were evaluated for solubility, viscosity, pH, and in vitro studies.Results: From FT-IR and DSC studies, it was confirmed that no chemical interaction existed between the drug and the natural polymers used. Solubility of glibenclamide was found to be 4.38 and 18.24 and atorvastatin calcium was found to be 6.84, 214.67, and 287.43 g/L. The viscosity of 1% w/v of locust bean gum, guar gum, and ghatti gum was found to be 169 cP, 124 cP, and 31 cP in distilled water. The pH of locust bean gum, guar gum, and gum ghatti solutions was found to be 5.6±0.49, 5.2±0.27, and 4.7±0.51. The in vitro studies suggested that glibenclamide pellets had shown a sustained release till 12 h, while atorvastatin calcium had shown immediate release of drug due to rapid disintegration of pellets.Conclusion: Thus, MUPS can be considered as an alternative approach to treat diabetes induced dyslipidemia

FORMULATION AND DEVELOPMENT OF IN SITU FORMING GEL FOR THE TREATMENT OF ORAL THRUSH

Objective: The objective of the present work was to develop an in situ gel composed of Pluronic F-127, Carbopol 934, and methylparaben and loaded with fluconazole using DoE software to sustain the delivery of drug in the buccal cavity.Methods: In situ gels were prepared by temperature-induced method, by employing DoE and characterized by Fourier transform infrared (FTIR), differential scanning calorimeter (DSC), and evaluated for gelation temperature, gelation time, adhesive force, and in vitro diffusion studies.Results: Both FTIR and DSC studies suggested that there were no chemical interactions present between both drug and polymers. The formulated gels S1, S3, and S9 showed gelation at a body temperature. The viscosity, gel strength, and mucoadhesive force for the formulated in situ gels were found to be within the ranges of 375–738 cps, 35–62 s, and 4650–5210.32 dynes/cm2, respectively. The in vitro diffusion studies indicated that optimized in situ gel S3 exhibited the improved ability to sustain the drug compared to other formulations.Conclusion: Thus, developed in situ gel system was determined to be effective in terms of eradication of oral thrush

RESEARCH AND DEVELOPMENT IN WOUND MANAGEMENT PRODUCTS: A BRIEF REVIEW

Wound can be defined as any process which leads to the disruption of the normal architecture of a tissue. They may be closed or open, for example, abrasions, lacerations, avulsions, ballistic and excised, or surgical wounds. Successful wound care includes advancing patient local and systemic conditions in conjunction with a perfect injury healing condition. Numerous wide assortments of dressing materials are accessible both for extreme and persistent non-healing wounds. A wide range of wound healing products have been produced to impact this injury condition to give a non-pathogen, ensured, and clammy region for healing to happen. A perfect injury dressing ought to limit loss of protein, electrolytes, and liquids from twisted and to diminish pain and contamination alongside wound healing. More current products are as of now being utilized to supplant or enlarge different substrates in the injury healing period. There is a sharp complexity to prior routine of wound administration, where the injury is permitted to dry, yet the present advancement was to move forward to the idea of wet injury recovering. This review of the present wounding periphery in wound recovery occurs at the most recent utilizations of silver and the employments of negative pressure wound gadgets, propelled dressings and skin substitutes, and biologic injury items including development of hydrogels and hyperbaric oxygen as an aid in wound mending. With the advancement of accessible dressings, the objective is to locate the most proper methodology or blend of modalities to optimize wound healing

Encapsulation of Lornoxicam into spermaceti microspheres and comparative bioavailability study

In this study, Lornoxicam (LX) loaded spermaceti (SC) microspheres were prepared using meltable emulsified dispersion cooling induced solidification technique and the bioavailability of the marketed product (Flexispaz® capsule-reference-product A) was compared with the optimized formulation (lornoxicam loaded spermaceti microspheres–test–product B). Morphological studies of wax microspheres were evaluated using scanning electron microscopy (SEM). The SEM images showed the spherical shape of wax microspheres and more than 97% of the isolated microspheres were in the size range 309-317 μm. Differential scanning calorimetry (DSC), Fourier transforms infrared (FTIR) spectroscopy and stability studies showed that the drug after encapsulation with SC microspheres was stable and compatible. A single dose, randomized, complete cross over study of LX (8mg) microspheres were carried out on 10 healthy male and female Albino sheep’s under fasting conditions. Plasma LX concentrations and other pharmacokinetic parameters obtained were statistically analyzed. Based on this study, it can be concluded that drug loaded LX microspheres and Flexispaz® capsule are bioequivalent in term of the rate and extent of absorption.Key words: Lornoxicam; Wax microspheres; Release kinetics; Bioavailability; Bioequivalence

FORMULATION DEVELOPMENT AND EVALUATION OF ALMOND GUM BASED SUSTAINED RELEASE MATRIX TABLET OF INDOMETHACIN

Objective: The aspiration of the current research involves employing various concentrations of polymer and filler to develop indomethacin sustained release (SR) matrix tablets. The objective of this research work is to reduce dosing frequency thereby increasing patients compliance and enhanced therapeutic activity.Methods: Polymers such as Almond gum (AG), polyvinylpyrrolidone (PVP), and starch at different concentrations were used for formulating SR polymeric matrix tablets. Evaluation of pre-compression and post-compression parameters was done for both granules and formulated tablets.Results: Results obtained from pre-compression parameters and post-compression parameters suggested that all the parameters are within the prescribed limits, demonstrating that formulated granules had shown better flow properties. The morphological characteristics of the developed tablet were observed by employing scanning electron microscope where the surface of the tablet was found to be smooth from the in vitro dissolution study, combination of AG (30 mg) with PVP (30 mg), and starch used as a filler has sustained the release of drug up to 10 h.Conclusion: Therefore, developed polymeric matrix tablet exhibited enhanced potency over a conventional tablet by exhibiting an excellent dissolution profile for a period of 10 h

FORMULATION AND INVESTIGATION OF POLYMERIC MULTIPLE UNIT PELLET SYSTEMS CONSISTING OF SUSTAINED RELEASE GLIMEPIRIDE AND IMMEDIATE RELEASE ATORVASTATIN CALCIUM

Objective: The objective of the present work was to develop novel fixed-dose combinations (FDCs) for improvement of glucose tolerance in type II diabetes mellitus patients associated with dyslipidemia. Methods: Multiple unit pellet systems (MUPSs) consisting of sustained release (SR) glimepiride and immediate release atorvastatin calcium pellets were formulated. The SR glimepiride pellets were prepared using a combination of locust bean gum and gum ghatti/guar gum. Similarly, the immediate release of atorvastatin calcium pellets was prepared using locust bean gum suspension as a binder. Results: The formulated pellets were characterized using Fourier transform infrared spectroscopy (FTIR) and Differential scanning calorimetry (DSC). Further, surface morphology of the formulated pellets was done by scanning electron microscopy (SEM). FT-IR and DSC studies suggested that there were no chemical interactions between the drug and natural polymers. SEM studies revealed that formulated pellets were in spherical shape. Based on in vitro evaluation, the SR glimepiride formulation developed using a combination of 2% locust bean gum and 2.5% gum ghatti polymers sustained the release of the drug up to 12 h. Similarly, the immediate release atorvastatin calcium formulation containing 1% w/w locust bean gum suspension as a binder and 7% croscarmellose sodium showed fast disintegration of pellets. The in vivo studies in albino Wistar rat revealed that there was an improvement in bioavailability of the drugs. Stability studies showed that there were no significant changes in the drug content and physical appearance of the prepared SR glimepiride and immediate release atorvastatin pellet formulations. Conclusion: Thus, the formulated FDC as MUPS can be used as an alternative approach for treating diabetes mellitus-induced dyslipidemia

DESIGNING OF COUMARIN DERIVATIVES AS SQUALENE SYNTHASE INHIBITORS

Objective: The importance of this research work is to design a library of novel coumarin derivatives by docking evaluation of the designed coumarin derivatives as squalene synthase inhibitor.Methods: The three-dimensional structure of designed molecules of squalene synthase inhibitors was collected from Protein Data Bank. The designed molecules were docked onto the enzymes that are squalene synthase inhibitor - 3WCM, 3WCJ, and 3Q2Z protein using SYBYL-X 2.1. Using a standard protocol, the protein was subjected to minimization and protomol generation.Results: By this method, we visualized the possible binding and also estimated the protein interactions with our intended coumarin library, using SYBYL-X 2.1 software. Into the active site of the selected enzymes, all the 20 coumarins were docked and then the docking scores revealed that the compounds possess high affinity toward the selected enzymes.Conclusion: With the help of virtual evaluation, we have elaborated a fast synthetically accessible coumarin-based compounds, and it is an advanced and original scaffold in the area of probable human squalene synthase inhibitors. Some of the developed compounds show better binding property than ligand, and in 3q2Z, the compound 5d shows better binding property than the protein. Furthermore, 6g and 6c have good binding property. In 3 WCM, the compound 6f has better property. In 3 WCJ, the compounds 6g and 6f show better binding property than the protein

Encapsulation of Lornoxicam into spermaceti microspheres and comparative bioavailability study

In this study, Lornoxicam (LX) loaded spermaceti (SC) microspheres were prepared using meltable emulsified dispersion cooling induced solidification technique and the bioavailability of the marketed product (Flexispaz® capsule-reference-product A) was compared with the optimized formulation (lornoxicam loaded spermaceti microspheres–test–product B). Morphological studies of wax microspheres were evaluated using scanning electron microscopy (SEM). The SEM images showed the spherical shape of wax microspheres and more than 97% of the isolated microspheres were in the size range 309-317 μm. Differential scanning calorimetry (DSC), Fourier transforms infrared (FTIR) spectroscopy and stability studies showed that the drug after encapsulation with SC microspheres was stable and compatible. A single dose, randomized, complete cross over study of LX (8mg) microspheres were carried out on 10 healthy male and female Albino sheep’s under fasting conditions. Plasma LX concentrations and other pharmacokinetic parameters obtained were statistically analyzed. Based on this study, it can be concluded that drug loaded LX microspheres and Flexispaz® capsule are bioequivalent in term of the rate and extent of absorption.Key words: Lornoxicam; Wax microspheres; Release kinetics; Bioavailability; Bioequivalence

The dental calculus metabolome in modern and historic samples.

INTRODUCTION: Dental calculus is a mineralized microbial dental plaque biofilm that forms throughout life by precipitation of salivary calcium salts. Successive cycles of dental plaque growth and calcification make it an unusually well-preserved, long-term record of host-microbial interaction in the archaeological record. Recent studies have confirmed the survival of authentic ancient DNA and proteins within historic and prehistoric dental calculus, making it a promising substrate for investigating oral microbiome evolution via direct measurement and comparison of modern and ancient specimens. OBJECTIVE: We present the first comprehensive characterization of the human dental calculus metabolome using a multi-platform approach. METHODS: Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) quantified 285 metabolites in modern and historic (200 years old) dental calculus, including metabolites of drug and dietary origin. A subset of historic samples was additionally analyzed by high-resolution gas chromatography-MS (GC-MS) and UPLC-MS/MS for further characterization of metabolites and lipids. Metabolite profiles of modern and historic calculus were compared to identify patterns of persistence and loss. RESULTS: Dipeptides, free amino acids, free nucleotides, and carbohydrates substantially decrease in abundance and ubiquity in archaeological samples, with some exceptions. Lipids generally persist, and saturated and mono-unsaturated medium and long chain fatty acids appear to be well-preserved, while metabolic derivatives related to oxidation and chemical degradation are found at higher levels in archaeological dental calculus than fresh samples. CONCLUSIONS: The results of this study indicate that certain metabolite classes have higher potential for recovery over long time scales and may serve as appropriate targets for oral microbiome evolutionary studies