Abdel-Azim Zaghloul

Bioavailability assessment of vitamin A self-nanoemulsified drug delivery systems in rats: a comparative study.

Objectives: To assess and compare the bioavailability of three different oral dosage forms of vitamin A in rats. The formulations included vitamin A self-nanoemulsified drug delivery (SNEDD) optimized formulation-filled capsule (F1), vitamin A SNEDD optimized formulation compressed tablet (F2) and vitamin A oily solution-filled capsules without any additives (control, F3). Materials and Methods: Bioavailability was assessed after a single oral dose of the three formulations using three groups of rats, each group comprising 6 rats. Blood samples were collected at baseline and over the next 8 h. Plasma was separated and extracted to obtain the drug, which was measured by HPLC. Statistical data analysis was performed using the Student t test and ANOVA with p < 0.05 as the minimal level of significance. Results: From the pharmacokinetic parameters, both F1 and F2 showed improved bioavailability compared to F3. The values of AUC ± SD were 3,080.7 ± 190.2, 2,137.1 ± 130.5 and 1,485.2 ± 80.1 ng·h/ml for F1, F2 and F3, respectively. The Tmax was 1 h in case of F1 and F2 as compared to 1.5 h for F3. The Cmax ± SD was 799.5 ± 48.5, 656.2 ± 64.4 and 425.8 ± 33.1 for F1, F2 and F3, respectively. The increase in AUC, Cmax and Tmax was significant (p < 0.05). The bioavailability calculated from the AUC for F1 and F2 relative to F3 was 207.4 and 143.8%, respectively. The bioavailability increased almost twofold and 1.4 times for F1 and F2, respectively. Conclusions: The study showed that the newly developed vitamin A SNEDD formulations increased the rate and extent of drug absorption compared to the oily drug solution. The present investigation demonstrated that vitamin A SNEDD optimized formulations, either as filled capsules or as compressed tablets, were superior to its oily solution with regard to their biopharmaceutical characteristics.

Biodegradable Microparticulates of Beta-Estradiol: Preparation and In Vitro Characterization

ABSTRACT Beta-estradiol has been recommended for the long-term therapy of osteoporosis and its oral formulations are subjected to intensive first pass metabolism. The present investigation was aimed at preparing and characterizing biodegradable microparticles of beta-estradiol with polymers such as PLA, PLGA 85/15, PLGA 75/25, and their mixtures. The microparticles were prepared by solvent evaporation method using methylene chloride as a solvent and polyvinyl alcohol as a surfactant. The drug-polymer ratios were 1:3, 1:5, and 1:7. The prepared microparticles (twelve formulations) were tested for encapsulation efficiency and in vitro drug release in 50% methyl alcohol/phosphate buffer pH 7.4. The results showed that the encapsulation efficiency varied from 81 to 100% and the formulation fabricated from PLGA 85/15 (1:3) showed less burst and consistent long time release. This formulation when further characterized displayed irregular spherical shape with an average particle size of 72 µm. The crystallinity of the drug was reduced when investigated using X-ray diffractometry. No chemical interaction between the drug and the polymer was observed as evidenced by FT-IR analysis. The results indicated that beta-estradiol biodegradable microparticles with PLGA 85/15 (1:3) could be a suitable approach for long term therapy of osteoporosis.

Physicochemical characterization of gliclazide–macrogol solid dispersion and tablets based on optimized dispersion

Background: This study investigated the physical interaction of gliclazide (GLC) with a hydrophilic carrier, that is, macrogol [polyethylene glycol (PEG)]. Different molecular weights of PEG (4000, 10,000, and 20,000) were used in different drug : carrier weight ratios (1 : 1, 1 : 2, 1 : 5, and 1 : 10). Method: Preliminary screening was done by phase solubility studies to characterize the liquid state interaction between the drug and the carrier. Solid dispersions (SDs) of GLC and PEG in different ratios were prepared by fusion technique and by physical mixing. The solid-state interaction between the drug and the carrier was examined by performing differential scanning calorimetry and Fourier transform infrared spectroscopic studies. SD with satisfactory characteristics was selected for the formulation of tablets by wet granulation method and compared with the commercial brand for in vitro dissolution. Results: It was evident from phase solubility studies that the drug solubility increased linearly with increasing PEG concentrations. In vitro dissolution of GLC improved significantly in the SDs prepared by fusion method as compared with the original drug and physical mixtures. Scanning electron microscopy images showed well-defined changes in the surface topography of GLC, thus confirming the effective formation of a fused binary system. The SD tablets showed a significant improvement in the drug release profile than that of the commercial brand. Conclusion: It was thus concluded that SD formulations of GLC can be successfully used to design a solid dosage form of the drug, which would have significant advantages over the current marketed tablets.

Response Surface Methodology to Obtain β-Estradiol Biodegradable Microspheres for Long-Term Therapy of Osteoporosis

The purpose of this work was to evaluate the main and interaction effects of formulation factors on the drug encapsulation efficiency of β-estradiol biodegradable microspheres by applying response surface methodology. A secondary purpose was to obtain an optimized formula for long-term therapy of osteoporosis. A three factor, three level Box-Behnken experimental design was used to get 15 experimental runs. The independent variables were drug/polymer ratio (X1), dispersing agent concentration (X2), and deaggregating agent concentration (X3). The dependent variables were percentage encapsulation efficiency (Y1), cumulative percent drug released (Y2), and percentage yield of the microspheres (Y3). The formulations were prepared by emulsion solvent evaporation technique using ethyl acetate as organic solvent. The optimized formulation was maximized for encapsulation efficiency and further characterized for the particle size distribution, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR). The mathematical relationship obtained between X1, X2, X3, and Y1 was: Y1 = −129.85 + 29.35X1 + 129.99X2 + 64.82X3 − 3.2X1X2 − 0.29X1X3 − 35.83X2X3 − 2.05X12 − 13.23X22 − 5.92X32 (R2 = 0.99) The equation showed that X1, X2, and X3 affect Y1 positively but interaction between any two of these factors affects Y1 negatively. The most significant interaction was between X2 and X3. The finding indicated that controlled releases β-estradiol biodegradable microspheres with high encapsulation efficiency and low pulsatile release can be prepared and the quantitative response surface methodology applied helped in understanding the effects and the interaction effects between the three factors applied.

Development of Novel Formulations to Enhance in Vivo Transdermal Permeation of Tocopherol

Tocopherol represents a big challenge for transdermal permeation owing to its extreme hydrophobicity and large molecular mass. The aim of the present study was to develop alpha-tocopherol (T) topical formulations and evaluate their ex vivo and in vivo permeation. Franz diffusion cells were used for ex vivo permeation, and neonatal rats were used for in vivo permeation. Seven gel formulations and 21 liquid formulations were investigated for physical stability, viscosity and permeation of T. Analysis of T was performed by a validated HPLC method using a UV detector. The ex vivo permeation from gel and emulsion formulations was very poor (0.001-0.015 %). Highest permeation was observed from monophasic liquid formulations containing dimethyl sulfoxide (DMSO), tocopheryl polyethylene glycols (TPGs), propylene glycol, ethanol and 9.5 % T. The in vivo results demonstrated higher retention in the epidermis compared to subcutaneous tissues, 1377 and 1.13 μg g-1, respectively. Increasing T concentration from 4.8 to 9.5 % did not increase the amount permeated or % of T retained. It was concluded that simple solutions of T in the presence of DMSO and TPGs were more promising systems for effective transdermal permeation compared to gel, emulsion or oleaginous systems.

Preparation and in vitro/in vivo evaluation of metformin hydrochloride rectal dosage forms for treatment of patients with type II diabetes

Abstract Background: Metformin hydrochloride (MtHCL) is an oral antidiabetic drug and has many other therapeutic benefits. It has poor bioavailability, narrow absorption window and extensive liver metabolism. Moreover, children and elders face difficulty to swallow the commercial oral tablets. Objectives: Preparation, in vitro/in vivo evaluation of MtHCL suppositories for rectal administration to solve some of these problems. Methods: Suppository fatty bases (Witepsol®, Suppocire® and Massa®; different grades) and PEG bases 1000, 4000 and 6000 (different ratios), were used to prepare rectal suppository formulations each containing 500 mg drug. These were characterized for manufacturing defects, and pharmacotechnical performance and formulations showing superior results were subjected to bioavailability testing in human volunteers compared with the commercial oral tablet (Ref) applying LC–MS/MS developed analytical technique. Results: The preparation method produced suppositories with satisfactory characteristics and free of manufacturing defects. The fatty bases were superior compared with PEG bases regarding the physical characteristics. Three formulations were chosen for bioavailability testing and the results showed comparable bioavailability compared to the Ref. Conclusions: The fatty bases showed superior characteristics compared with the PEG bases. MtHCL formulated in selected fatty bases could be a potential alternative to the commercial oral tablets particularly for pediatric and geriatric patients.

In vitro and in vivo Permeation of Vitamin E and Vitamin E Acetate from Cosmetic Formulations

Objective: To investigate the ability of α-tocopherol acetate (TA) and α-tocopherol (T), widely used ingredients in cosmetics, to cross the epidermal barrier using the neonatal rat as a model. Materials and Methods: The content of T and TA in four marketed products (A–D) and two experimental formulations (F1, F2) was investigated by HPLC. An in vitro permeation study was performed in neonatal rat epidermis using diffusion cells. In vivo permeation was studied in neonatal rats after repeated application of the products and analysis of T and TA in the stratum corneum/deeper skin layers. Results: Variable contents of TA were found in the marketed products (0.12–0.53%). No vitamin permeation was detected through the stratum corneum as in vitro biological barrier after 4 h. No detectable T and TA were seen in the in vivo permeation study in the epidermis. Variable degrees of drug penetration (4.3–12.6%) of the applied dose into the deeper skin layers were observed, depending on the formulation. In vivo application of TA-containing preparations did not result in any transformation of TA into T under the described experimental conditions. Conclusion: TA and T exhibited variable skin penetration and TA did not transform into T under the experimental conditions. The data underscored the need for further studies to optimize such formulations to improve vitamin E transdermal permeation and eventually achieve the expected cosmetic/therapeutic outcome.