Mahmoud El-Badry

Improvement of solubility and dissolution rate of indomethacin by solid dispersions in Gelucire 50/13 and PEG4000.

The aim of this study was to prepare and characterize solid dispersions of water insoluble non-steroidal anti-inflammatory drug, indomethacin (IND), with polyethylene glycol 4000 (PEG4000) and Gelucire 50/13 (Gelu.) for enhancing the dissolution rate of the drug. The solid dispersions (SDs) were prepared by hot melting method at 1:1, 1:2 and 1:4 drug to polymer ratios. Scanning electron microscopy (SEM), X-ray powder diffractometry (XRD) and differential scanning calorimetry (DSC) were used to examine the physical state of the drug. Furthermore, the solubility and the dissolution rate of the drug in its different systems were explored. The data from the XRD showed that the drug was still detectable in its solid state in all SDs of IND-Gelu. and disappeared in case of higher ratio of IND-PEG4000. DSC thermograms showed the significant change in melting peak of the IND when prepared as SDs suggesting the change in crystallinity of IND. The highest ratio of the polymer (1:4) enhanced the drug solubility about 4-folds or 3.5-folds in case of SDs of IND-PEG or IND-Gelu., respectively. An increased dissolution rate of IND at pH 1.2 and 7.4 was observed when the drug was dispersed in these carriers in form of physical mixtures (PMs) or SDs. IND released faster from the SDs than from the pure crystalline drug or the PMs. The dissolution rate of IND from its PMs or SDs increased with an increasing amount of polymer.

Enhancement of the Dissolution and Permeation Rates of Meloxicam by Formation of Its Freeze-dried Solid Dispersions in Polyvinylpyrrolidone K-30

ABSTRACT Freeze-drying (FD) and solvent evaporation (SE) were used to prepare solid dispersions (SDs) of meloxicam (MX) in polyvinylpyrrolidone K-30 (PVP). The SDs were prepared at different ratios, namely 1:1, 1:3, and 1:5 MX:PVP weight ratio. Differential scanning calorimetry (DSC), infrared absorption spectroscopy (IR), and x-ray powder diffractometry (XPD) were utilized to characterize the physicochemical properties of the SDs. Meloxicam (MX) in the solid dispersions appeared with less crystallinity form and was present in a complete amorphous form at higher PVP ratio. Dissolution rates of MX as a pure drug, physical mixtures (PMs), and SDs indicated a marked increase of the dissolution rate of MX in presence of PVP. The increase in the dissolution rate was dependent on the ratio of PVP and the method of preparation. In addition, the permeability of the drug through standard cellophane membrane and hairless mouse skin was also evaluated. The permeation rate of MX was significantly increased in the case of SDs and was dependent on the ratio of PVP. The results were primarily due to increase wettability, the solubilization of the drug by the carrier, and formation of MX amorphous form.

The use of spray-drying to enhance celecoxib solubility

The present research investigates the enhancement of the dissolution rate of celecoxib by using spray-drying to prepare a solid dispersion with various polymers, namely Kollicoat IR® (Kollicoat), polyvinyl alcohol (PVA) 22000, or polyethylene glycol 6000 (PEG). The investigated drug-to-polymer mass ratios were 1:1, 1:2, and 1:4 by weight. Hydroalcoholic or methylene chloride solvent systems were used. The obtained yields ranged from 65% to 78%, whereas the entrapment efficiencies were between 68% and 82%. The results revealed an increase in the dissolution rate of the prepared particles up to 200% within 20 min. The prepared particles were investigated using differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The increased dissolution rate was attributed to hydrogen bond formation between celecoxib and each polymer together with the reduced size of the formed particles offering a greater overall surface area. It was concluded that spray-drying may be considered a successful one-step technique to improve the dissolution rate of celecoxib when using Kollicoat, PVA, or PEG as the carrier polymer.

Preparation and Characterization of Spironolactone-Loaded Gelucire Microparticles Using Spray-Drying Technique

The basic objectives of this study were to prepare and characterize solid dispersions of poorly soluble drug spironolactone (SP) using gelucire carriers by spray-drying technique. The properties of the microparticles produced were studied by differential scanning calorimetry (DSC), scanning electron microscopy, saturation solubility, encapsulation efficiency, and dissolution studies. The absence of SP peaks in DSC profiles of microparticles suggests the transformation of crystalline SP into an amorphous form. The in vitro dissolution test showed a significant increase in the dissolution rate of microparticles as compared with pure SP and physical mixtures (PMs) of drug with gelucire carriers. Therefore, the dissolution rate of poorly water-soluble drug SP can be significantly enhanced by the preparation of solid dispersion using spray-drying technique.

Comparative topical delivery of antifungal drug croconazole using liposome and micro-emulsion-based gel formulations

Abstract The aim of this study was to develop liposomal-based (LBGF) and micro-emulsion-based (MBGF) gel formulations of croconazole to compare their topical delivery potential. Conventional gels were also prepared using various polymers such as sodium carboxymethyl cellulose (SCMC), Poloxamer 407, Carbopol 971P and chitosan. The in vitro release of croconazole from conventional gel formulations, LBGF and MBGF were carried out using cellophane membrane as permeation membrane. However, in vitro skin permeations studies of all formulations were carried out using rat skin. The results of the drug release/skin permeation studies indicated that the highest release was obtained from SCMC followed by chitosan, Poloxamer 407 and finally Carbopol 971P gel. Therefore, liposomes and micro-emulsions were loaded on Carbopol 971P gel. The drug release and skin permeation of croconazole from different LBGF and MBGF showed that MBGF had superior release/permeation than LBGF. MBGF having ethanol as co-surfactant showed higher release/permeation of drug than MBGF-containing propylene glycol. The analysis of data according to different kinetic models indicated that the release of drug from different LBGF and MBGF followed the Higuchi model. The antimicrobial activity of the different LBGF and MBGF of croconazole was carried out by measuring the inhibition zone (mm) and compared by the effect of miconazole cream as control. The different LBGF and MBGF showed an excellent activity against different species of fungi as compared with miconazole cream. Overall, these results indicated that developed LBGF and MBGF could have great potential for topical delivery of croconazole.

Physicochemical Characterization and Dissolution Properties of Meloxicam-Gelucire 50/13 Binary Systems

A solid dispersion of Meloxicam (MX), a poorly soluble, non steroidal anti-inflammatory drug, and Gelucire 50/13 was prepared by spray drying. Spherical microparticles were yielded with smooth surfaces as observed by scanning electron microscopy. According to differential scanning calorimetry and powder X-ray diffractometry analysis, MX was transformed from the crystalline state to the amorphous state as confirmed by the disappearance of its melting peak and the crystalline peaks. The dissolution tests at pH 7.4 revealed that the dissolution rate of encapsulated MX was 2.5-fold higher than that of the corresponding physical mixture and fourfold higher than the drug alone, respectively. The microparticles prepared at a ratio of 1:4 (drug/Gelucire) exhibited a 4-fold higher anti-inflammatory activity on the paw edema of rats in comparison to the drug alone. All in all, this work reveals that spray drying is a suitable technique for preparation of solid dispersions with improved biopharmaceutical and pharmacological characteristics of MX.

Preparation, charactarization and anti-inflammatory activity of celecoxib chitosan gel formulations

This study was designed to evaluate the suitability of chitosan polymer as a vehicle for topical delivery system. Celecoxib, which is a nonsteroidal anti-inflammatory drug, was incorporated into the gel vehicles in a concentration of 0.5 % w/v. Gels were prepared using three different concentrations and different molecular weights of chitosan. Viscosity, drug release from gels, permeation of drug through rat skin and anti-inflammatory activity of the drug were studied. In vitro release characteristics of the drug from different gels were carried out using dialysis membrane in phosphate buffer using a pH of 6.8. The results showed that, the gel form containing 1.0 % w/v medium molecular weight chitosan has superior drug release than other forms, whilst the gel form containing 2.0 % w/v high molecular weight chitosan shows the lowest amount of drug release. The release data were treated with various kinetic principles to assess the relevant parameters. The results revealed an inverse correlation between the percent drug release and the polymer concentration used. The results also showed that the release of drug from the prepared gels obeyed the Higuchi’s diffusion model. The permeation of drug through rat skin was carried out. The flux of drug is independent on the viscosity of the formulae. The anti-inflammatory activity of the drug in different gel formulations was studied using carrageenan-induced rat paw edema method. The results obtained show that there is excellent anti-inflammatory activity of the gel forms on rat paw edema.

Effects of Kollicoat IR and hydroxypropyl-beta-cyclodextrin on the dissolution rate of omeprazole from its microparticles and enteric-coated capsules.

Omeprazole microparticles were prepared by different drying techniques using Kollicoat IR® and hydroxypropyl-β-cyclodextrin hydrophilic polymers. Physico-chemical properties were investigated using differential scanning calorimetry and powder X-ray diffractometry. Dissolution rate was determined and compared to the physical mixtures and the morphology was studied using a scanning electron microscope. Omeprazole transformed from the crystalline state to the amorphous state as confirmed by the disappearance of its melting peak and the characteristic of the crystalline peaks. Omeprazole dissolution rate was enhanced significantly from its spray- and freeze-dried microparticles as compared to the corresponding physical mixtures and drug alone (P < 0.05). F3 and F5 formula possessed superior release rate over other formulations. In acidic medium, the release of drug from enteric-coated capsules was not detectable, while it is completely released within 40 min after changing dissolution medium to phosphate buffer (pH 7.4). The transformation of OME from crystalline to amorphous state by using either Kollicoat IR® or hydroxylpropyl-β-cyclodextrin is considered a promising way to improvement of drug dissolution.

Transdermal delivery of meloxicam using niosomal hydrogels: in vitro and pharmacodynamic evaluation

Abstract Non-ionic surfactant vesicles were prepared using Span-60 and cholesterol in the mass ratios of 1:1, 2:1, 1:2 and 3:1 for transdermal delivery of an anti-inflammatory drug meloxicam (MXM). The drug encapsulation efficiencies and particle size were observed in the range of 32.9–80.7% and 56.5–133.4 nm, respectively. Three different gel bases were also prepared using Poloxamer-407, Chitosan and Carbopol-934 as polymers to study the performance of the in vitro release of the drug. Prepared gels were also converted into niosomal gels. In vitro release characteristics of MXM from different gels were carried out using dialysis membrane in phosphate buffer (pH 7.4). The poloxamer-407 gel or niosomal poloxamer-407 gel showed the superior drug release over the other formulations. The release data were treated with various mathematical models to assess the relevant parameters. The results showed that the release of MXM from the prepared gels and niosomal gels followed Higuchi’s diffusion model. The flux of MXM was found to be independent on the viscosity of the formulations. The anti-inflammatory effects of MXM from different niosomal gel formulations were evaluated using carrageenan-induced rat paw edema method, which showed superiority of niosomal gels over conventional gels.

Properties of solid dispersion of piroxicam in Pluronic F-98

A solid dispersion approach (SD) has been developed to enhance the dissolution properties of insoluble drugs by improving their aqueous solubility. An insoluble drug, piroxicam (PXM), was dispersed in a water-soluble carrier, Pluronic F-98 (Pl. F-98). Different methods were employed to prepare such dispersion, namely: the solvent method (SM), the melting method (MM), the melting-solvent method (MSM), the co- grinding method (GM) and the kneading method (KM). Solid dispersion obtained using the solvent method was prepared using different solvents, namely: methylene chloride, acetone and chloroform. Different tools were used, to characterize the prepared solid dispersion, such as the infrared spectroscopy (IR), the powder X-ray diffractometry (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The dissolution rate from the prepared SDs was determined in simulated gastric fluid and was found in the following order: KM > MM > GM > PM (physical mixture) > SM > MSM > PXM. Solubility of the free and of the dispersed drug was determined at different temperatures and solution heats were calculated. The results revealed that solubility of the dispersed drug was markedly enhanced by the rise in temperature. From this study, the increased dissolution rate in systems containing Pl. F-98 was probably the result of increased wettability and dispersibility, as well as particle size reduction of PXM and decrease in the crystalline fraction of the drug, since no interaction could be demonstrated between PXM and Pl. F-98.