Nahla S. Barakat

Carbamazepine uptake into rat brain following intra-olfactory transport

Targeting the brain via nasal administration of drugs has been studied frequently over the last few years. In this study, a suitable gel formulation was designed to provide the absorption of a highly lipophilic drug through nasal mucosa. For this purpose, carbamazepine was chosen as the model drug. Hypromellose and Carbopol were used as mucoadhesive polymers in the formulation to increase the residence time of the gel on the mucosa. The objective of this study was to confirm the existence of a transport pathway for a drug (carbamazepine) to the brain directly from the nasal cavity, by comparing the concentration of drug in the brain after intranasal (i.n.), intravenous (i.v.), and oral (p.o.) administration. A statistically significant high level of the drug was found in the brain following intranasal administration compared with the intravenous and oral routes. These findings suggested the existence of a direct transport pathway for carbamazepine from the nasal cavity to the brain. This pathway may represent a new delivery route to the brain and central nervous system of such drugs which are needed in high and rapid concentration in the brain, especially in emergencies.

Controlled-release carbamazepine matrix granules and tablets comprising lipophilic and hydrophilic components

The objective of this study was to investigate the effect of lipophilic (Compritol® 888 ATO) and hydrophilic components (combination of HPMC and Avicel) on the release of carbamazepine from granules and corresponding tablet. Wet granulation followed by compression was employed for preparation of granules and tablets. The matrix swelling behavior was investigated. The dissolution profiles of each formulation were compared to those of Tegretol® CR tablets and the mean dissolution time (MDT), dissolution efficiency (DE%), and similarity factor (f2 factor) were calculated. It was found that increase in the concentration of HPMC results in reduction in the release rate from granules and achievement of zero-order is difficult from the granules. The amount of HPMC plays a dominant role for the drug release. The release mechanism of CBZ from matrix tablet formulations follows non-Fickian diffusion shifting to Case II by the increase of HPMC content, indicating significant contribution of erosion. Increasing in drug loading resulted in acceleration of the drug release and in anomalous controlled-release mechanism due to delayed hydration of the tablets. These results suggest that wet granulation followed by compression could be a suitable method to formulate sustained release CBZ tablets.

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.

In Vitro Characterization of Carbamazepine-Loaded Precifac Lipospheres

Lipospheres of carbamazepine were prepared by melt dispersion technique using Precifac® ATO 5 in the various drug-lipid ratios. The resulting free-flowing lipospheres were evaluated with respect to surface morphology, particle size distribution, encapsulation efficiency, and in vitro release behavior. The effect of druglipid ratio, the surfactant added, emulsion stabilizer, and stirring speed also were identified as the key variables affecting the formation of discrete spherical lipospheres and drug release rate. The preparation conditions were optimized by using 0.4% w/v span 20 (Hydrophilic-Lipophilic Balance, HLB=8.6) as a surfactant and 1% w/v gelatin solution as a stabilizer in presence of a high level of water.We found that the ratio of drug to lipid affects the size of the spheres. The incorporation efficiency was found to be high at all loadings. Increasing the lipid:drug ratio produced more spherical, smooth, and round lipospheres. All the prepared lipospheres exhibited slow release profiles dictating the Higuchi mode of release. We saw that the higher the sphere size and the ratio of Precifac®, the slower is in vitro drug release.

Enhanced oral bioavailability of etodolac by self-emulsifying systems: in-vitro and in-vivo evaluation

Objectives The objective of this study was to prepare a self‐emulsifying drug delivery system (SEDDS) for oral bioavailability enhancement of a poorly water‐soluble drug, etodolac. The SEDDS formulations were optimized by evaluating their ability to self‐emulsify when introduced to an aqueous medium under gentle agitation, and by determination of the particle size of the resulting emulsion.

Diclofenac sodium loaded-cellulose acetate butyrate: Effect of processing variables on microparticles properties, drug release kinetics and ulcerogenic activity

The aim of this study was to develop and characterize diclofenac sodium loaded-cellulose acetate butyrate microparticles in order to obtain a controlled-release system. The influence of the type of polymer, the volume and composition of the internal phase, drug loading, surfactant concentration and additive added on microparticles characteristics (particle size, encapsulation efficiency, surface morphology and in vitro release profiles) was studied to optimize the microparticles system. The resultant microparticles were evaluated for the recovery, average particle size, drug loading and incorporation efficiency. The microparticles exhibited good flowing nature and compressibility index when compared to pure drug. Dissolution rate of diclofenac sodium in phosphate buffer (pH 6.8) increased with increases in initial drug loading, surfactant concentration and addition of alcohol as co-solvent but decreased with increases in the concentration of additives such as Gantrez® AN or Eudragit S100 in the internal phase. The dissolution data showed a Higuchi diffusion pattern for most of the formulations. About 56–81% reduction in ulcerogenic activity was observed with microparticles containing Eudragit S100 17–25%, based on total polymer concentration, when compared with pure diclofenac sodium.

Evaluation of Glycofurol-Based Gel as a New Vehicle for Topical Application of Naproxen

In view of the good skin tolerability, glycofurol was used as a vehicle-based gel, and its effect in the topical penetration of Naproxen (NAP) was investigated. The aims of this study were to develop a suitable gel with bioadhesive property, spreadability, and viscosity for topical anti-inflammatory effect. Three gelling and adhesive agents were examined: Carbopol 974P, Gantrez AN 119, and polyvinylpyrollidone K30. Skin permeation rates and lag times of NAP were evaluated using the Franz-type diffusion cell in order to optimize the gel formulation. The permeation rate of NAP-based gel across the excised rat skin was investigated. A significant increase in permeability parameters such as steady-state flux (Jss), permeability coefficient (Kp), and penetration index (PI) was observed in optimized formulation containing 2% Transcutol as an permeation enhancer. From skin irritation test, it was concluded that the optimized novel glycofurol-based gel formulation was safe to be used for topical drug delivery. The developed glycofurol-based gel appeared promising for dermal and transdermal delivery of naproxen and could be applicable with water-insoluble drugs, which would circumvent most of the problems associated with drug therapy.

Controlled-release carbamazepine granules and tablets comprising lipophilic and hydrophilic matrix components.

The objective of this study was to investigate the effect of lipophilic (Compritol® 888 ATO) and hydrophilic components (combination of HPMC and Avicel) on the release of carbamazepine from granules and corresponding tablet. Wet granulation followed by compression was employed for preparation of granules and tablets. The matrix swelling behavior was investigated. The dissolution profiles of each formulation were compared to those of Tegretol® CR tablets and the mean dissolution time (MDT), dissolution efficiency (DE %) and similarity factor (f2 factor) were calculated. It was found that increase in the concentration of HPMC results in reduction in the release rate from granules and achievement of zero-order is difficult from the granules. The amount of HPMC plays a dominant role for the drug release. The release mechanism of CBZ from matrix tablet formulations follows non-Fickian diffusion shifting to case II by the increase of HPMC content, indicating significant contribution of erosion. Increasing in drug loading resulted in acceleration of the drug release and in anomalous controlled-release mechanism due to delayed hydration of the tablets. These results suggest that wet granulation followed by compression could be a suitable method to formulate sustained release CBZ tablets.

Design and development of gliclazide-loaded chitosan microparticles for oral sustained drug delivery: in-vitro/ in-vivo evaluation

Objectives  The objective of this study was to prepare gliclazide–chitosan microparticles with tripolyphosphate by ionic crosslinking.

In vitro and in vivo characteristics of a thermogelling rectal delivery system of etodolac.

Rectal etodolac–Poloxamer gel systems composed of Poloxamer and bioadhesive polymers were developed and evaluated. Hydroxypropylmethyl cellulose, poly)vinyl) pyrrolidone, methyl cellulose, hydroxyethylcellulose, and carbopol were examined as mucoadhesive polymers. The characteristics of the rectal gels differed according to the properties of mucoadhesive polymers. The physicochemical properties such as gelation temperature, gel strength, and bioadhesive force of various formulations were investigated. The analysis of release mechanism showed that the release of etodolac was proportional to the square root of time, indicating that etodolac might be released from the suppositories by Fickian diffusion. The anti-inflammatory effect of etodolac–Poloxamer gel system was also studied in rats. Moreover, liquid suppository of etodolac did not cause any morphological damage to the rectal tissues. These results suggested that in situ gelling liquid suppository with etodolac and mucoadhesive polymer was a physically safe, convenient, and effective rectal dosage form for etodolac.