ENHANCEMENT OF LORNOXICAM SOLUBILITY BY INCLUSION COMPLEXATION WITH CYCLODEXTRIN: PREPARATION AND CHARACTERIZATION

Objective: Lornoxicam is a potent anti-inflammatory drug which has analgesic and antipyretic properties. It is water-insoluble powder. The inclusion complexes of lornoxicam (LOR) with β-cyclodextrin (βCD) and 2-hydroxypropyl-β-cyclodextrin (HPCD) were prepared and characterised in order to improve the solubility of the drug and enhance its bioavailability.Methods: Complexes were prepared by physical mixing and freeze-drying in three different drug/polymer ratios (1:1, 1:2 and 3:2). The solid complexes were characterised through differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray diffraction, nuclear magnetic resonance (NMR) spectroscopy, and Fourier transformed infrared (FTIR) spectroscopy.Results: The data showed that LOR may be complexed with cyclodextrin (CD) forming soluble complexes. The lyophilized 1:2 LOR/HPCD complex is the most soluble.Conclusion: Solubility increases with lyophilization than with physical mixing and by the use of HPCD than βCD in complexation

EFFECT OF BIODEGRADABLE CO-POLYMERS AND DIVALENT CATIONS ON THE SUSTAINED RELEASE ABILITY OF PROPRANOLOL HYDROCHLORIDE LOADED BIOMATERIAL MICROSPHERES

Objective: Propranolol Hydrochloride (PHCL) is used for the treatment of hypertension and angina pectoris; however it has two major problems; short biological halfâ€life and low bioavailability, so the aim of the present work was to develop PHCL mucoadhesive microsphere to prolong the residence time at the absorption site, therefore, increase the bioavailability.Methods: PHCL microspheres were prepared by ionotropic gelation method using nature polymers. Factorial design (33) was used to develop PHCL mucoadhesive microspheres, the independent factors used were polymer type (Sodium carboxymethyl cellulose (Na CMC), and Hydroxyl propyl methyl cellulose (HPMC), Carpobol 940), cross-linking type (calcium chloride, zinc chloride and barium chloride) and the concentration of Chitosan (0.5, 1, 1.5 %w/v). The developed microspheres were physicochemical characterized. The selected formula was selected for mucoadhesive test and in vivo study on human volunteers.Results: The results revealed that the PHCL mucoadhesive microspheres have good flowability, the mean particle sizes ranged from 541 to 815 µm and the entrapment efficiency ranged from 35.6% to 69.53%. The selected PHCL microspheres showed spherical particles with a rough surface and exhibited a slow release over 8h. The pharmacokinetic data of selected PHCL microspheres showed prolonged Tmax, decreased Cmax and AUC0–∞ value of 926.21±40.74ng. h/ml indicating improved relative bioavailability by144.93% compared with marketed tablets.Conclusion: PHCL microspheres were successfully prepared by ionic gelatin method that retards the release and enhances the oral bioavailability.Keywords: Propranolol HCL, Microspheres, Ionic gelation method, Chitosan, Relative bioavailabilit

Innovative pulmonary targeting of terbutaline sulfate-laded novasomes for non-invasive tackling of asthma: statistical optimization and comparative in vitro/in vivo evaluation.

Asthma represents a globally serious non-communicable ailment with significant public health outcomes for both pediatrics and adults triggering vast morbidity and fatality in critical cases. The β2-adrenoceptor agonist, terbutaline sulfate (TBN), is harnessed as a bronchodilator for monitoring asthma noising symptoms. Nevertheless, the hepatic first-pass metabolism correlated with TBN oral administration mitigates its clinical performance. Likewise, the regimens of inhaled TBN dosage forms restrict its exploitation. Consequently, this work is concerned with the assimilation of TBN into a novel non-phospholipid nanovesicular paradigm termed novasomes (NVS) for direct and effective TBN pulmonary targeting. TBN-NVS were tailored based on the thin film hydration method and Box-Behnken design was applied to statistically optimize the formulation variables. Also, the aerodynamic pattern of the optimal TBN-NVS was explored via cascade impaction. Moreover, comparative pharmacokinetic studies were conducted using a rat model. TBN elicited encapsulation efficiency as high as 70%. The optimized TBN-NVS formulation disclosed an average nano-size of 223.89 nm, ζ potential of −31.17 mV and a sustained drug release up to 24 h. Additionally, it manifested snowballed in vitro lung deposition behavior in cascade impactor with a fine particle fraction of 86.44%. In vivo histopathological studies verified safety of intratracheally-administered TBN-NVS. The pharmacokinetic studies divulged 3.88-fold accentuation in TBN bioavailability from the optimum TBN-NVS versus the oral TBN solution. Concisely, the results proposed that NVS are an auspicious nanovector for TBN pulmonary delivery with integral curbing of the disease owing to target specificity

Establishing Clonal Cell Lines with Endothelial-Like Potential from CD9(hi), SSEA-1(−) Cells in Embryonic Stem Cell-Derived Embryoid Bodies

BACKGROUND: Differentiation of embryonic stem cells (ESCs) into specific cell types with minimal risk of teratoma formation could be efficiently directed by first reducing the differentiation potential of ESCs through the generation of clonal, self-renewing lineage-restricted stem cell lines. Efforts to isolate these stem cells are, however, mired in an impasse where the lack of purified lineage-restricted stem cells has hindered the identification of defining markers for these rare stem cells and, in turn, their isolation. METHODOLOGY/PRINCIPAL FINDINGS: We describe here a method for the isolation of clonal lineage-restricted cell lines with endothelial potential from ESCs through a combination of empirical and rational evidence-based methods. Using an empirical protocol that we have previously developed to generate embryo-derived RoSH lines with endothelial potential, we first generated E-RoSH lines from mouse ESC-derived embryoid bodies (EBs). Despite originating from different mouse strains, RoSH and E- RoSH lines have similar gene expression profiles (r(2) = 0.93) while that between E-RoSH and ESCs was 0.83. In silico gene expression analysis predicted that like RoSH cells, E-RoSH cells have an increased propensity to differentiate into vasculature. Unlike their parental ESCs, E-RoSH cells did not form teratomas and differentiate efficiently into endothelial-like cells in vivo and in vitro. Gene expression and FACS analysis revealed that RoSH and E-RoSH cells are CD9(hi), SSEA-1(−) while ESCs are CD9(lo), SSEA-1(+). Isolation of CD9(hi), SSEA-1(−) cells that constituted 1%–10% of EB-derived cultures generated an E-RoSH-like culture with an identical E-RoSH-like gene expression profile (r(2) = 0.95) and a propensity to differentiate into endothelial-like cells. CONCLUSIONS: By combining empirical and rational evidence-based methods, we identified definitive selectable surface antigens for the isolation and propagation of lineage-restricted stem cells with endothelial-like potential from mouse ESCs

Physiologically compatible cardiac assist device and method

US20030176760A1Published Applicatio

Nanosized soy phytosome-based thermogel as topical anti-obesity formulation: an approach for acceptable level of evidence of an effective novel herbal weight loss product

Shahira F El-Menshawe,1 Adel A Ali,1 Mohamed A Rabeh,2 Nermeen M Khalil3 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni Suef, 2Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Giza, 3Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Nahda University Beni-Suef, Beni Suef, Egypt Purpose: Herbal supplements are currently available as a safer alternative to manage obesity, which has become a rising problem over the recent years. Many chemical drugs on the market are designed to prevent or manage obesity but high cost, low efficacy, and multiple side effects limit its use. Nano lipo-vesicles phytosomal thermogel of Soybean, Glycine max (L.) Merrill, was formulated and evaluated in an attempt to investigate its anti-obesity action on body weight gain, adipose tissue size, and lipid profile data. Methods: Three different techniques were used to prepare phytosome formulations including solvent evaporation, cosolvency, and salting out. The optimized phytosome formulation was then selected using Design Expert® (version 7.0.0) depending on the highest entrapment efficiency, minimum particle size (PS), and maximum drug release within 2 hours as responses for further evaluation. The successful phytosome complex formation was investigated by means of Fourier-transform infrared spec­troscopy and determination of PS and zeta potential. Phytosome vesicles’ shape was evaluated using transmission electron microscope to ensure its spherical shape. After characterization of the optimized phytosome formulation, it was incorporated into a thermogel formulation. The obtained phytosomal thermogel formulation was evaluated for its clarity, homogeneity, pH, and gel transformation temperature besides rheology behavior and permeation study. An in vivo study was done to investigate the anti-weight-gain effect of soy phytosomal ther­mogel. Results: EE was found to be >99% for all formulations, PS ranging from 51.66–650.67 while drug release was found to be (77.61–99.78) in range. FTIR and TEM results confirmed the formation of phytosome complex. In vivo study showed a marked reduction in body weight, adipose tissue weight and lipid profile.Conclusion: Concisely, soy phytosomal thermogel was found to have a local anti-obesity effect on the abdomen of experimental male albino rats with a slight systemic effect on the lipid profile data. Keywords: soy, Glycine max, lipase, phytosomal thermogel, topical delivery, natural treatment&nbsp

A novel transdermal nanoethosomal gel of betahistine dihydrochloride for weight gain control: in-vitro and in-vivo characterization

Shahira F El-Menshawe,1 Adel Ahmed Ali,1 Abdelkhalk Ali Halawa,2 Ahmed SG Srag El-Din2 1Department of Pharmaceutics and Industrial Pharmacy, Beni-Suef University, Beni-Suef, 2Department of Pharmaceutics and Clinical Pharmacy, Nahda University, Beni-Suef, Egypt Background: Betahistine dihydrochloride (BDH) is a histamine analog used to control weight gain, with short elimination half-life and gastric irritation as side effects.Objective: The aim of the current investigation is to formulate and optimize a topical BDH ethosomal gel for weight gain control.Materials and methods: Box–Behnken design was applied to study the effect of independent variables: phosphatidylcholine (PC), propylene glycol (PG), and ethanol on vesicle size; entrapment efficiency; % drug release; and flux. The morphology and zeta potential of the optimized formulation were evaluated. The % drug release, flux, and pharmacodynamics of the optimized formulation gel were studied.Results: The size and entrapment efficiency percent had a direct positive relationship with the concentration of PC and negative relationship with ethanol and PG. The % drug release and flux decreased with increasing PC and PG, while ethanol enhanced both responses. Regression modeling indicated a good correlation between dependent and independent variables, where F16 was chosen as the optimized formulation. F16 showed well-defined spherical vesicles and zeta potential of −24 mV, and % release from the gel exceeded 99.5% over 16 h with the flux of 0.28 mg/cm2/h. Food intake and weight gain of rats were significantly decreased after transdermal application of the BDH ethosomal gel when compared with control, placebo, and BDH gel. The histopathological findings proved the absence of inflammation and decrease in adipose tissue.Conclusion: Results obtained showed a significant, sustained transdermal absorption of BDH ethosomal gel and, consequently, a decrease in food intake and weight gain. Keywords: Box–Behnken design, regression modeling, neural histamine, pharmacodynamics, obesit

NOVEL GASTRO-RETENTIVE POLYMERIC MICROSPHERES: AN APPROACH FOR INCREASED BIOAVAILABILITY AND AN ONCE DAILY DOSING OF TERBUTALINE SULPHATE

Objective: The purpose of this study was to develop multi-unit alginate-copolymer adhesive microspheres to achieve a sustained release of terbutaline sulphate (TBS) and overcome the hepatic first pass effect so as to enhance its bioavailability.Methods: The microspheres were prepared using inotropic gelation method and different concentration of sodium alginate alone or in combination with other polymers as well as using chitosan as a coating polymer in some formulations. All of the prepared microspheres were evaluated for yield, size, encapsulation efficiency, in vitro release and mucoadhesivity. The selected formulations (F11 and F19) were further subjected to differential scanning calorimetry, Fourier transform infrared spectroscopy, stability and in vivo bioavailability studies.Results: The prepared microspheres exhibited quite widely varying encapsulation efficiencies from 20 to 74. 8 % and its mean diameter was in range of 963. 3-1. 635 µm. The in vitro release study showed a sustained release profile. The selected formulations were further subjected to differential scanning calorimetry and FTIR which confirm the absence of any incompatibility. X-ray diffraction suggests the amorphous nature of the drug after encapsulation. The selected formulation F11 and F19 showing encapsulation efficiency higher than 55 %, an amount of drug released within 50-60 % after 8 h and a relative bioavailability of 283. 84 % and 202. 04 % respectively compared with the marketed oral Aironyl® tablets.Conclusion: The prepared microspheres were significantly efficient to achieve a sustained release of terbutaline sulphate with a higher relative bioavailability in comparison with the oral marketed tablet