Formulation and Evaluation of Mucoadhesive in-Situ Nasal Gel of Tapentadol Hydrochloride

Tapentadol Hydrochloride is a Tapentadol is a centrally acting analgesic. It has 33% bioavailability due to its first pass effect and hence possesses problems in the development of oral sustained release formulations. Mucoadhesive thermo reversible in-situ nasal gel of Tapentadol HCl was designed and developed to sustain its release due to the increased nasal residence time of the formulation. Poloxamer 407 (PF 127) was selected as it has excellent thermo sensitive gelling properties. HPMCK4M was added to impart mucoadhesive to the formulation, and PEG 400 was used to enhance the drug release. 32 Factorial designs were employed to assess the effect of concentration of HPMCK4M and PEG 400 on the performance of in-situ nasal gel systematically and to optimize the formulation. An optimized in-situ nasal gel was evaluated for appearance, pH, drug content, gelation temperature, mucoadhesive force, viscosity and ex-vivo permeability of drug through nasal mucosa of a goat. Additionally, this formulation was proved to be safe as histopathological studies revealed no deleterious effect on nasal mucosa of a goat after prolonged exposure of 21 days to the optimized formulation. Thus the release of Tapentadol Hydrochloride can be sustained if formulated in an in-situ nasal gel containing poloxamer 407 to achieve its prolonged action.

FORMULATION, DEVELOPMENT AND IN-VITRO EVALUATION OF A BAMBUTEROL HYDROCHLORIDE IN-SITU GELLING SYSTEM FOR NASAL DELIVERY

The goal of this project was to design, develop, and in-vitro evaluation of an in-situ gelling system for nasal administration of Bambuterol hydrochloride. All of the batches were prepared using different concentration of pectin, given different doses of simulated nasal electrolyte solution (SNES) i.e., 0.1 ml to 2.0 ml. All batches and formulation batches with a composition of 0.8 percent low methoxyl pectin underwent an in vitro gelation testing. The pH of the formulation reduced as the pectin content increased due to the acidic nature of pectin. The drug concentration was greater than 95%, and the apparent viscosity of the sol and gel was measured using a Brookfield viscometer (Rotational Viscometer Model). When the concentration of gelling polymer was increased from 0.5 to 1.0 percent, the gel strength (SOL) increased from 0.6 to 1 sec. The gel strength (GEL) increased from 0.7 to 13 seconds as a result of gelation. In vitro drug release experiments showed that the resulting formulations could release the medication for up to 10 hours when Higuchi kinetics were applied to all of them. The gels were stable across the six-month test period, according to the accelerated stability studies. There was no drug-polymer interaction, according to DSC and XRD analyses. Based on these findings, in situ nasal gel could be a possible drug delivery strategy for bambuterol hydrochloride, allowing it to bypass first-pass metabolism and hence improve bioavailability.

DEVELOPMENT OF RIVASTIGMINE LOADED SELF ASSEMBLED NANOSTRUCTURES OF NONIONIC SURFACTANTS FOR BRAIN DELIVERY

Objective: Aim of the study is to develop rivastigmine-loaded niosomal in situ gel via the intranasal route to the brain by crossing the Blood-Brain Barrier. For the treatment of Alzheimer’s disease, it provides a speedy onset of action, a faster therapeutic effect, avoidance of the first-pass metabolism, and enhanced bioavailability. Methods: Rivastigmine niosomal in situ nasal gel was developed, refined and tested with the goal of delivering the medicine to the brain via the intranasal route Rivastigmine niosomes were formulated by thin-film hydration technique, optimized using (32) factorial design and characterized for its physicochemical parameters. Rivastigmine-loaded niosomes were further incorporated into Carbopal-934P and HPMC-K4M liquid gelling system to form in situ nasal gel. The resulting solution was evaluated for several parameters including, viscosity at pH 5 and pH 6, gelling capacity and gelling time. Results: Optimized best formulation containing span 60 (A) and cholesterol (B) with (1:0.5) ratio identified from the model developed from Design-Expert®12 software, exhibited Entrapment efficiency (76.5±0.23%), particle size (933.4±0.14 nm), in vitro drug release maximum (68.94±0.26%) at 8th hour and further studied for its characteristics by SEM and TEM showed stable vesicles. Polynomial equations of Y1, Y2, and Y3 were conducted and ANOVA results showed a significant impact (p<0.05) on three levels. In vivo perfusion studies using rat model showed, the niosomes developed has good perfusion compared to pure drug with 27.2% of drug absorption in the brain at the end of 3 h. In vitro permeation of Rivastigmine through the dialysis membrane showed that 60.74% w/w drug permeated after 8 h. The formation of stable vesicles was proved by Zeta potential measurements and SEM analysis. Conclusion: Optimized formulation had greater perfusion and was expected to have a good bioavailability compared to conventional other drug delivery systems.

Design and development of zolmitriptan niosomal in situ nasal gel for the treatment of migrain

The objective of the present study was to development of Zolmitriptan (ZMT) niosomal in situ nasal gel formulation for migraine treatment. By intranasal route delivered drug to the central nervous system (CNS) through the olfactory lobes, which bypasses the first-pass metabolism and consequently enhances the bioavailability. Noisome of ZMT were prepared by using the lipid film hydration method. Optimized niosomal formulation was used to prepare in situ gel. The developed Noisomal formulations were characterized for vesicle size, shape, zeta potential, entrapment efficiency, drug content and in-vitro diffusion study, mucoadhesive strength, permeation study, FTIR, DSC and XRD studies. The FTIR and DSC studies predicted that there was no any interaction in drug and excipients. ZMT niosomes were showed particle size, Polydispersity index (PDI), Zeta potential, % entrapment efficiency and drug content, 149nm, 0.223, -28.9, 88.16±0.8 % and 96.23±1.2% respectively. In-vitro diffusion study of niosomes shows 96.23±0.7% at 8h. The permeation rate of in situ niosomes gel and the pure drug was about 98.56% and 79.46%, respectively. XRD & DSC studies were showed that reduce crystalinity in the formulations. The SEM images of niosomes were found spherical in shape to some extent showing particle size distribution. Thus, it can be concluded that developed ZMT niosomal in situ gel formulation can be considered as a promising system for which may reduce dose requirement, improve patient acceptability and efficient targeting drug delivery to the brain through the olfactory lobe for migraine treatment.

Formulation and Characterization of Tranylcypromine loaded Polymeric Micellar In-Situ Nasal Gel for treatment of Depression

:Tranylcypromine is a drug used as antidepressant,anxiolytic, nonselective MAO A/B inhibitor. This drug is used to treat depression.The research was conducted to develop a polymeric micelle using a block copolymer, Pluronic F-68 and Gelucire 50/13 to improve the permeability of Tranylcypromine (TCP). A direct dissolution method was used to prepare polymeric micelles. The prepared micelles were characterised for particle size, % EE, zeta potential, in-vitro release. These micelles solution was used to prepare in situ gel by cold method in order to achieve controlled release. Central composite design was used for optimization of both polymeric micelles and insitu nasal gel.The main objective of this research work is to develop formulation acting centrally without undergoing first pass metabolism i.ie. directly nasal to brain delivery route.