Mamdouh M. Ghorab

Tablet formulation containing meloxicam and β-cyclodextrin: Mechanical characterization and bioavailability evaluation

The purpose of this research was to evaluate β-cyclodextrin (β-CD) as a vehicle, either singly or in blends with lactose (spray-dried or monohydrate), for preparing a meloxicam tablet. Aqueous solubility of meloxicam in presence of β-CD was investigated. The tablets were prepared by direct compression and wet granulation techniques. The powder blends and the granules were evaluated for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to thickness, diameter, weight variation test, drug content, hardness, friability, disintegration time, and in vitro dissolution studies. The effect of β-CD on the bioavailability of meloxicam was also investigated in human volunteers using a balanced 2-way crossover study. Phase-solubility studies indicated an AL-type diagram with inclusion complex of 1∶1 molar ratio. The powder blends and granules of all formulations showed satisfactory flow properties, compressibility, and drug content. All tablet formations prepared by direct compression or wet granulation showed acceptable mechanical properties. The dissolution rate of meloxicam was significantly enhanced by inclusion of β-CD in the formulations up to 30%. The mean pharmacokinetic parameters (Cmax, Ke, and area under the curve [AUC]0−∞) were significantly increased in presence of β-CD. These results suggest that β-CD would facilitate the preparation of meloxicam tablets with acceptable mechanical properties using the direct compression technique as there is no important difference between tablets prepared by direct compression and those prepared by wet granulation. Also, β-CD is particularly useful for improving the oral bioavailablity of meloxicam.

Nanostructured lipid carriers (NLCs) versus solid lipid nanoparticles (SLNs) for topical delivery of meloxicam

Abstract Objective: The aim of this study was to develop nanostructured lipid carriers (NLCs) as well as solid lipid nanoparticles (SLNs) and evaluate their potential in the topical delivery of meloxicam (MLX). Materials and methods: The effect of various compositional variations on their physicochemical properties was investigated. Furthermore, MLX-loaded lipid nanoparticles-based hydrogels were formulated and the gels were evaluated as vehicles for topical application. Results and discussion: The results showed that NLC and SLN dispersions had spherical shapes with an average size between 215 and 430 nm. High entrapment efficiency was obtained ranging from 61.94 to 90.38% with negatively charged zeta potential in the range of −19.1 to −25.7 mV. The release profiles of all formulations exhibited sustained release characteristics over 48 h and the release rates increased as the amount of liquid lipid in lipid core increased. Finally, Precirol NLC with 50% Miglyol® 812 and its corresponding SLN were incorporated in hydrogels. The gels showed adequate pH, non-Newtonian flow with shear-thinning behavior and controlled release profiles. The biological evaluation revealed that MLX-loaded NLC gel showed more pronounced effect compared to MLX-loaded SLN gel. Conclusion: It can be concluded that lipid nanoparticles represent promising particulate carriers for topical application.

A Transdermal Delivery System for Glipizide

Glipizide is one of the most commonly prescribed drugs for treatment of type 2 diabetes. Oral therapy with glipizide comprises problems of bioavailability fluctuations and may be associated with severe hypoglycaemia and gastric disturbances. As a potential for convenient, safe and effective antidiabetic therapy, the rationale of this study was to develop a transdermal delivery system for glipizide. For this purpose, inclusion complexes of the drug in beta-cyclodextrin (beta-CyD), dimethyl-beta-cyclodextrin (DM-beta-CyD), hydroxypropyl-beta-cyclodextrin (HP-beta-CyD), and hydroxypropyl-gamma-cyclodextrin (HP-gamma-CyD) were prepared. Several percutaneous formulations of the drug and the prepared complexes in different bases (o/w emulsion, polyethylene glycol, carboxymethyl cellulose and Carbopol) were developed. Release studies revealed an improved release of the drug from formulations containing glipizide-CyD complexes. Ex vivo permeation studies through full thickness rat abdominal skin were conducted, whereby the effect of several conventional penetration enhancers (propylene glycol [PG], oleic acid, urea, dimethyl sulfoxide, menthol, limonene and cineole) was monitored. Highest flux was obtained from ointments prepared with Carbopol gel base containing a combination of PG and oleic acid as well as ointments prepared in the same base utilizing glipizide-DM-beta-CyD complex and urea. In vivo studies on diabetic male Wistar rats revealed a marked therapeutic efficacy sustained for about 48 hours. In this respect, two formulations showed best biological performance. In the first formulation, the drug was incorporated in Carbopol gel base in the presence of 20% PG together with 15% oleic acid. The second was prepared by incorporating glipizide-DM-beta-CyD complex in Carbopol gel base in presence of 15% urea. The glucose tolerance test showed suppression of hyperglycaemia induced in glucose-loaded rats. The above-mentioned results might shed a strong beam of light on the feasibility of using glipizide in a transdermal delivery system for treatment of type 2 diabetes with the aim of improving both patient compliance and pathophysiology of the disease.

SOLID LIPID NANOPARTICLES FOR TOPICAL DELIVERY OF MELOXICAM: DEVELOPMENT AND IN VITRO CHARACTERIZATION

Isolated NPCs are able to proliferate in response to basic fibroblast growth factor and when the culture conditions are altered means addition of BDNF and NT-3, they differentiate into several phenotypes of neurons. Fabricated PCL with 10% sucrose and 10% PEG 4000 scaffold shown good proliferation rate upto 14 days while PCL with 5% sucrose shown to promote good cells attachement and survival rate more than 21 days this may be due to pore size & pore number.

Novel Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Oral Delivery of Olmesartan Medoxomil: Design, Formulation, Pharmacokinetic and Bioavailability Evaluation.

The main purpose of this study was to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) of Olmesartan (OLM) for enhancement of its solubility and dissolution rate. In this study, liquid SNEDDS containing Olmesartan was formulated and further developed into a solid form by the spray drying technique using Aerosil 200 as a solid carrier. Based on the preliminary screening of different unloaded SNEDDS formulae, eight formulae of OLM loaded SNEEDS were prepared using Capryol 90, Cremophor RH40 and Transcutol HP as oil, surfactant and cosurfactant, respectively. Results showed that the mean droplet size of all reconstituted SNEDDS was found to be in the nanometric range (14.91–22.97 nm) with optimum PDI values (0.036–0.241). All formulae also showed rapid emulsification time (15.46 ± 1.34–24.17 ± 1.47 s), good optical clarity (98.33% ± 0.16%–99.87% ± 0.31%) and high drug loading efficiency (96.41% ± 1.20%–99.65% ± 1.11%). TEM analysis revealed the formation of spherical and homogeneous droplets with a size smaller than 50 nm. In vitro release of OLM from SNEDDS formulae showed that more than 90% of OLM released in approximately 90 min. Optimized SNEDDS formulae were selected to be developed into S-SNEDDS using the spray drying technique. The prepared S-SNEDDS formulae were evaluated for flow properties, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), reconstitution properties, drug content and in vitro dissolution study. It was found that S-SNEDDS formulae showed good flow properties and high drug content. Reconstitution properties of S-SNEDDS showed spontaneous self-nanoemulsification and no sign of phase separation. DSC thermograms revealed that OLM was in solubilized form and FTIR supported these findings. SEM photographs showed smooth uniform surface of S-SNEDDS with less aggregation. Results of the in vitro drug release showed that there was great enhancement in the dissolution rate of OLM. To clarify the possible improvement in pharmacokinetic behavior of OLM S-SNEDDS, plasma concentration-time curve profiles of OLM after the oral administration of optimized S-SNEDDS formula (F3) were compared to marketed product and pure drug in suspension. At all time points, it was observed that OLM plasma concentrations in rats treated with S-SNEDDS were significantly higher than those treated with the drug in suspension and marketed product.

Effect of Antiadherents on the Physical and Drug Release Properties of Acrylic Polymeric Films

Antiadherents are used to decrease tackiness of a polymer coating during both processing and subsequent storage. Despite being a common excipient in coating formulae, antiadherents may affect mechanical properties of the coating film as well as drug release from film-coated tablets, but how could addition of antiadherents affect these properties and to what extent and is there a relation between the physical characteristics of the tablet coat and the drug release mechanisms? The aim of this study was to evaluate physical characteristics of films containing different amounts of the antiadherents talc, glyceryl monostearate, and PlasACRYLTM T20. Eudragit RL30D and Eudragit RS30D as sustained release polymers and Eudragit FS30D as a delayed release material were used. Polymer films were characterized by tensile testing, differential scanning calorimetry (DSC), microscopic examination, and water content as calculated from loss on drying. The effect of antiadherents on in vitro drug release for the model acetylsalicylic acid tablets coated with Eudragit FS30D was also determined. Increasing talc concentration was found to decrease the ability of the polymer films to resist mechanical stress. In contrast, glyceryl monostearate (GMS) and PlasACRYL produced more elastic films. Talc at concentrations higher than 25% caused negative effects, which make 25% concentration recommended to be used with acrylic polymers. All antiadherents delayed the drug release at all coating levels; hence, different tailoring of drug release may be achieved by adjusting antiadherent concentration with coating level.

Optimization of Gabapentin Release and Targeting Absorption, Through Incorporation into Alginate Beads

Aims: 1) To study the effect of some formulation variables on drug load, encapsulation efficiency, swelling ratio, mucoadhesion and drug release. 2) Optimize the mucoadhesion capabilities for targeting drug absorption and releasecontrolling capabilities of algi nate beads. Methodology: Alginatebeads were prepared by dripping sodium alginate gel into calcium chloride solution and then dried overnight at ambient temperature. The effects of alginate concentration, cross linker concentration, cross linking time, vol

Effects of Glycerides on the Intestinal Absorption of Cyclosporine A Using the In-Situ Mesenteric Vein Cannulated Rat Model

The purpose of this study was to evaluate and compare the effect of glycerides with different fatty acid distributions (e.g. Arlacel 186, Capmul GMO and Captex 350) on Cyclosporine absorption in rat ileum segment using the modified single-pass intestinal perfusion with mesenteric vein cannulation. Drug concentration in the perfusate and blood plasma was analyzed by HPLC; and permeability coefficients were calculated from drug appearance in blood (P(blood)) and disappearance from perfusate (P(lumen)). Particle size was measured using Malvern Zetasaizer 1000HSA. Rheologic properties were measured using Brookfield viscometer. The results show that the average particle sizes after dilution (100 folds) of formulae containing Arlacel 186, Capmul GMO and Captex 350 and containing 0.8 mM CsA were 260+/-35.8, 130+/-11.4 and 37.5+/-6.0 nm, respectively. The polydispersity index was 0.6, 0.7 and 0.108 for formulations with Arlacel 186, Capmul GMO and Captex 350, respectively. CsA permeability coefficients (P(blood)) calculated from drug appearance in the blood in presence of Arlacel 186, Capmul GMO and Captex 350 were 0.3x10(-6), 1.0x10(-6) and 1.7x10(-6) cm2/sec, respectively. Phenol red was used as a water marker to determine net water absorption and secretion. Its constant concentration suggested that formulation did not alter intestinal water flux. From the results we can conclude that degree of glyceride esterification has a potential impact on the average particle size distribution and polydispersity of the formed micelles on dilution, which on turn contribute to the interaction between membrane and drug.

Diclofenac-induced Gastric Ulceration in Rats: Protective Roles of Pantoprazole and Misoprostol

Gastrointestinal damage caused by diclofenac remains a significant clinical problem. Pantoprazole provides potent and long-lasting inhibition of gastric acid secretion and has proven efficacy in healing diclofenac-associated ulcers, including those with continued exposure to diclofenac. The objective of this study was to prepare and evaluate microbeads of diclofenac sodium coated with sodium alginate and Hydroxypropylmethylcellulose (HPMC) in order to obtain controlled release drug delivery system. The ulcerogenic activity and histopathological effects of the prepared formulation were compared with a marked formula containing the drug with misoprostol which orally administered to male Wistar rats. Ionotropic gelation technique was the technique of choice to encapsulate the drug. IR spectral analysis indicated no interaction between the drug and polymers used. Microbeads which showed a significant reduction in the release of diclofenac at acidic pH of Original Research Article El-Deen et al.; BJPR, 11(3): 1-12, 2016; Article no.BJPR.24636 2 the stomach as well as maximal release at alkaline pH of the intestine were selected to conduct further in vivo evaluation. The beads were administered to rats in combination with pantoprazole. The obtained ulcer index as well as the histopathological effects of the proposed formulations was compared to marketed formula containing the drug combined with misoprostol. The obtained in vivo results indicate that administration of pantoprazole and diclofenac microbeads has shown efficacy in reducing the risk of GIT ulcerations compared with administration of misoprostol and diclofenac or diclofenac separately.

Simple Controlled Release Delivery System for an Anti-hypertensive Drug via Buccal Route

Objective: This study aims to develop controlled release buccal tablets of losartan potassium based on bioadhesion using direct compression technique. Materials and Methods: The bioadhesive buccal tablets of losartan potassium were prepared after preliminary drug -excipients compatibility studies and micromeretics study for powder blends. The tablets were prepared by direct compression utilizing carbopol 934LR as a primary bioadhesive polymer either with or without chitosan or hydroxypropyl methylcellulose E15LV as secondary polymers. Other excipients included PVP K30 as a binder, magnesium stearate as a lubricant and mannit ol as a diluent. The tablets were evaluated for weight variation, thickness and diameter, hardness, friability, drug content, surface pH,Ex-vivoresidence time and bioadhesion force,In-vitroswelling anddrug release study.The analysis of the release pr ofiles in the light of distinct kinetic models