ZIPRASIDONE HYDROCHLORIDE LOADED NANOSTRUCTURED LIPID CARRIERS (NLCS) FOR INTRANASAL DELIVERY: OPTIMIZATION AND IN VIVO STUDIES

Objective: The present study was an attempt to systemically deliver the most desirable schizophrenia drug, ziprasidone hydrochloride (ZRS) via the intranasal route using nanostructured lipid carrier (NLC) approach. Methods: The desired ZRS loaded NLCs were developed using central composite statistical design and the developed formulation was monitored for improving ZRS bioavailability and their brain targeting efficacy. Results: Pharmacokinetic studies revealed a 10 fold increase (ZRS blood-brain ratio) for NLCs administered through nasal route (in comparison to intravenous route). Similarly, the concentration of ZRS (in the brain) delivered via nasal route exhibits 4 fold increment at all-time points. Conclusion: Therefore, the obtained results suggest a potential nose to brain transport of loaded ZRS by effective bypassing of the Blood-Brain Barrier (BBB)

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

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

FORMULATION AND EVALUATION OF ORAL DISINTEGRATING FILM OF ATENOLOL

Objective: The main objective of the study was to formulate the oral disintegrating films loaded with atenolol by solvent-casting method and to carry out its evaluation studies.Methods: The films were prepared using the film-forming hydrophilic polymer like hydroxypropyl methylcellulose (E-5) and super disintegrant like pectin in various proportions.The formulated oral films were characterized for Fourier transform infrared (FTIR) and morphological evaluations. Various physicochemical parameters such as weight variation, folding endurance, surface pH, in vitro disintegration, and in vitro dissolution studies were carried out.Results: FTIR studies revealed that there was no drug-polymer interaction. The morphological evaluation of films showed that all the films were homogenous and transparent. The folding endurance test ensured that the films had sufficient brittleness and by weight variation test, it was inferred that all the films were within the deviation. The surface pH study showed the pH of the films was around neutral pH. The drug was well distributed in all the films. The films disintegrated within 120 s and the fastest being disintegrated in 30 s. Based on all the evaluation parameters, F6 had shown optimal performance and remarkable increase in drug release of 94.38% in 2 min.Conclusion: Thus, formulated oral disintegrating films can be termed as an alternative approach to deliver atenolol

CANCER NANOTECHNOLOGY: NANOPARTICULATE DRUG DELIVERY FOR THE TREATEMENT OF CANCER

In 21st century scientist all around are trying to formulate the new drug delivery with better efficacy and effectiveness to treat cancer. So their focus has been shifted toward the Nano based drug delivery system because nanotechnology plays with the dimension of the matter typically on the 0.2-to 100-nm scale (Nano scale). When the matter is size reduced its properties changes this is because at the Nano scale the percentage of atoms at the surface of a material becomes more significant. The interesting part of nanotechnology is that when the matter is in bulk possess relatively constant physical properties regardless of their size, but at the Nano scale the matter behave in the different ways. This is because when the material becomes smaller the percentage of atoms at the surface increases relative to the total number of atoms of the material bulk. This can lead to unexpected properties of nanoparticles which are partly due to the surface of the material dominating over the bulk properties. Hence nanotechnology is playing a important role in developing better and effective drug delivery system to fight against cancer.Â