DEVELOPMENT OF FROVATRIPTAN SUCCINATE MICROEMULSION FOR NASAL DELIVERY: OPTIMIZATION, IN VITRO AND IN VIVO EVALUATION

Objective: The main objective of the present research work was to develop, optimize, and characterize microemulsion (ME) of frovatriptan succinate to improve brain transport. Methods: The pseudoternary phase diagrams were constructed for ME formulations composed of Capmul MCM, Cremophor EL, and propylene glycol. Frovatriptan succinate-loaded ME was optimized by simplex lattice design having the concentration of oil, surfactant, and cosurfactant representing three apex points on the triangle. These were taken as independent variables and percentage drug release as a response variable. All developed batches of ME were characterized for in vitro tests, histopathology study, and pharmacokinetics in Swiss albino rats. Results: Clear MEs were obtained. F5 having particle size – 142.0 nm, zeta potential – 17.7–−7.8 mv, refractive index – 1.38±0.20, drug content – 98.24±0.20%, and drug diffused through dialysis membrane – 85% was the optimized batch. Drug permeation through the nasal mucosa of F5 in the ex vivo study was found to be 82.32%. Histopathology microscopic study has shown that F5 does not cause any irritation and structural changes in sheep nasal mucosa. The pharmacokinetic parameters were determined after nasal and oral administration of F5. For brain tissue, after nasal administration were Cmax181±1.51 ng/ml, Tmax – 2±1.01, area under curve (AUC)0−6 – 390.0±2.08 ng.h/ml. The AUC0−6 attained by nasal ME was 3.29 times greater than oral solution. Drug targeting index of frovatriptan succinate was 2.06. This was found satisfactory. Conclusion: Microemulsion of said composition was found to be enhancing delivery of frovatriptan succinate to brain tissues through nasal route

DEVELOPMENT OF METOCLOPRAMIDE HYDROCHLORIDE IN SITU GEL: NASAL DELIVERY AND PHARMACOKINETICS IN NEW ZEALAND RABBITS

Objective: Systemic bioavailability of metoclopramide hydrochloride (MCH) is 32–80% by oral route. The study was targeted to develop in situ gel of MCH for nasal delivery and to study its pharmacokinetics in healthy rabbits. Pre-systemic metabolism can be overcome. Methods: Poloxamer 407 (P407) aqueous solutions were prepared by cold method. In 32 factorial design, independent variables were Carbopol 934P and polyethylene glycol 6000 (PEG 6000), and dependent responses were gelation temperature, mucoadhesive strength, and drug release. A Pharmacokinetic study was carried out in New Zealand rabbits. The optimized in situ gel (1 mg/ml) was compared with marketed Reglan® (2 mg/2 ml) injection. Area under the curve (AUC), Cmax, and Tmax were estimated. Results: F2 was an optimized formulation. The study showed that P407 solutions formed a gel at nasal temperature 34°C having mucoadhesive strength 806.12±3.45 dyne/cm2. MCH release was found to be 93.74±1.31% within 6 h. Histopathological examination of formulation F2 exhibited safety to the nasal mucosa. The pH of formulations was 5.1±0.1 to 5.6±0.1 in the range of pH of nasal cavity. Plasma samples were analyzed by liquid chromatography/mass spectroscopy (LC/MS). The area under curve AUC0-4 for in situ gel by nasal route was 2716±4.617 ng/h/ml and for marketed solution by intravenous route was 2874±1.0816 ng/h/ml. These were comparable. Nasal bioavailability was found 94.50% from in situ gel. Duration of action was longer, and steady-state concentration was found for in situ gel. Conclusion: In situ gel was capable to release MCH in systemic circulation. In vivo study in rabbits has proved the improved bioavailability of MCH administered nasally. The optimized gel preparation was found to be promising for improved bioavailability

DEVELOPMENT AND IN-VITRO EVALUATION OF QUANTUM DOTS AS A CARRIER FOR DELIVERY OF 5-FLUOROURACIL

Objective: The present study was aimed to develop and evaluate quantum dots (QDs) as a carrier for delivery of 5-fluorouracil (5-FU).Methods: This research work includes a synthesis, characterization and in vitro study of 5-fluorouracil (5-FU) QDs. Zinc oxide QDs were synthesized, and the drug was loaded on them. These QDs were further coated with Eudragit E PO to achieve drug release only at the acidic pH range as well as to overcome release of drug in the formulation vehicle itself.Results: For 5-FU QDs optimized batch, yield (74±0.001 %), drug loading (85.58±0.08 %) and drug content (95±0.015%) were observed. FTIR spectroscopy revealed no any incompatibility between drug, polymer and metal SEM images shown drug loaded QDs with rough surface and Eudragit E PO coated QDs with smooth surface. The DSC curve of 5-FU exhibits peak at 286 °C corresponding to its melting point and Eudragit E PO coated QDs exhibit peak at 272 °C. This shifting of the endotherm suggested possible interaction of 5-FU and Eudragit E PO coated QDs. The diffractogram of pure drug showed multi-crystalline nature. However pure Eudragit E PO showed amorphous nature. Optimized QDs showed the crystalline nature of the drug. Mean particle size of optimized formulation batch was 201.92 nm and zeta potential was found+1.85 mV.Conclusion: An Optimized batch of QDs has the potential to utilize in future for imaging of cancer cells and targeting delivery of 5-FU.Â

Overcoming Poor Solubility of Dimenhydrinate: Development, Optimization and Evaluation of Fast Dissolving Oral Film

Purpose: To develop fast dissolving oral film to address vomiting and nausea in pediatric population. Methods: Oral films of Dimenhydrinate were prepared by solvent casting method by using hydroxypropylmethyl cellulose E5 (HPMC E5), polyethylene glycol 400 (PEG 400) and croscarmellose sodium. Solubility of dimenhydrinate was enhanced by ethanol as a co-solvent. To make dimenhydrinate palatable sodium saccharin and peppermint oil were used. All films were evaluated for mechanical parameters, surface pH, morphology, disintegration time and percent dissolution. Results: Films were smooth, acceptable and white in colour. For optimized batch, drug content (99.106%), disintegration time (25 sec), dissolution (99.10% in 210 sec), surface pH (6.81) were acceptable. Conclusion: Optimized batch, due to its potential to deliver through fast dissolving film, can be developed for clinical use

Design and Evaluation of Polyherbal Nanogel for The Treatment of Rheumatoid Arthritis

A typical autoimmune condition known as rheumatoid arthritis is linked to progressive impairment, systemic problems, early death, and socioeconomic expenses. Rheumatoid arthritis has no known cause, and the prognosis is uncertain. However, new therapies with better results have been developed as a result of breakthroughs in our knowledge of the disease's aetiology. The current therapeutic approach, which reflects this advancement, involves starting intensive therapy shortly as a diagnosis is made and escalating the medication in the goal of clinical response while being guided by an evaluation of the disease condition. The medicinal industry is not an alternative to the increasing paradigm of nanotechnology, which is evoking advancements in practically all technological sectors. It has long been utilised for artificial medicine production. The emphasis today is on conventional therapies, though. This study has a considerable application in the developing field of nanomedicine because it focuses upon the nanogel preparations of conventional drugs. As the risks and shortcomings of contemporary medicine become more obvious, herbal therapies are experiencing a comeback because they are viewed as a fair and well-balanced method of therapy. The effectiveness of herbal medicines in the treatment and management of disease is demonstrated by developments in analytical and clinical studies. Herbal treatments' primary drawback is their failure to dissolve and stabilize. Newer technological developments may be able to solve the issues with herbal remedies. Nano-formulations show how modern technology and herbal medicines interact. Consequently, herbal medications' increased stability, homogeneity, low toxicity, and strong drug encapsulation capacities make them a promising candidate for innovative drug delivery systems

Investigation of Cyperus Rotundus Root Extract on Diabetic Complications in Rats with Alloxan-Induced Diabetes

Background and Introduction: The prevalence of hyperglycemic diseases known collectively as diabetes has reached epidemic proportions in the current century. Diabetics are particularly vulnerable to infections, which can have devastating health consequences. The purpose of this research was to examine the effects of an aqueous extract of Cyperus rotundus roots on diabetic complications in rats with diabetes caused by Alloxan. Martial and Methods: Specifically: Alloxan monohydrate, Borosilicate, and a diagnostic kit. Specifically: a diagnostic kit, a phrase, or a paraphrase. Centrifuge Micropippet, Glucose check monitoring device, electronic digital scales, EDDY's Hot plate analgesometer MK-11, and the Biofuse pico. All chemicals employed were of the AR grade variety, including the alloxan monohydrate, metformin, chloroform, diethyl ether, and ethyl ether.Results: No deaths or toxicity symptoms were observed in the AECR acute toxicity test in mice, indicating that the extract was well tolerated and the test doses were safe in the animals. The effect of AECR on fasting blood glucose level in alloxan-induced diabetic rats was measured using an auto analyzer glucose kit to determine the compound's antidiabetic activity. The plasma or blood glucose level is measured after an individual has fasted as part of a carbohydrate metabolic test. The hormone glucagon is secreted into the bloodstream during fasting to facilitate the catabolic release of glucose. Conclusion: The results show that in alloxan-induced diabetic rats, the oral administration of an aqueous extract of Cyperus rotundus exhibited neuroprotective, nephroprotective, and hepatoprotective activities by increasing insulin production and decreasing glucogan production and an SGOT snd SGPT level

DEVELOPMENT OF METOCLOPRAMIDE HYDROCHLORIDE IN SITU GEL: NASAL DELIVERY AND PHARMACOKINETICS IN NEW ZEALAND RABBITS

Objective: Systemic bioavailability of metoclopramide hydrochloride (MCH) is 32–80% by oral route. The study was targeted to develop in situ gel of MCH for nasal delivery and to study its pharmacokinetics in healthy rabbits. Pre-systemic metabolism can be overcome.&#x0D; Methods: Poloxamer 407 (P407) aqueous solutions were prepared by cold method. In 32 factorial design, independent variables were Carbopol 934P and polyethylene glycol 6000 (PEG 6000), and dependent responses were gelation temperature, mucoadhesive strength, and drug release. A Pharmacokinetic study was carried out in New Zealand rabbits. The optimized in situ gel (1 mg/ml) was compared with marketed Reglan® (2 mg/2 ml) injection. Area under the curve (AUC), Cmax, and Tmax were estimated.&#x0D; Results: F2 was an optimized formulation. The study showed that P407 solutions formed a gel at nasal temperature 34°C having mucoadhesive strength 806.12±3.45 dyne/cm2. MCH release was found to be 93.74±1.31% within 6 h. Histopathological examination of formulation F2 exhibited safety to the nasal mucosa. The pH of formulations was 5.1±0.1 to 5.6±0.1 in the range of pH of nasal cavity. Plasma samples were analyzed by liquid chromatography/mass spectroscopy (LC/MS). The area under curve AUC0-4 for in situ gel by nasal route was 2716±4.617 ng/h/ml and for marketed solution by intravenous route was 2874±1.0816 ng/h/ml. These were comparable. Nasal bioavailability was found 94.50% from in situ gel. Duration of action was longer, and steady-state concentration was found for in situ gel.&#x0D; Conclusion: In situ gel was capable to release MCH in systemic circulation. In vivo study in rabbits has proved the improved bioavailability of MCH administered nasally. The optimized gel preparation was found to be promising for improved bioavailability.</jats:p