Magda W. Samaha

In sight into tadalafil – block copolymer binary solid dispersion: Mechanistic investigation of dissolution enhancement

Tadalafil is a phosphodiesterase-5 inhibitor that is characterized by low solubility and high permeability. Solid dispersion approach represents a promising carrier system for effective enhancement of dissolution and oral bioavailability of poorly soluble drugs. In the present work, novel tadalafil-loaded solid dispersions employing various block copolymers (Pluronics(®)) were prepared through fusion technique. Their solubility and dissolution properties were compared to the drug alone. In order to elucidate the mechanism of dissolution enhancement, solid state characteristics were investigated using scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction. Furthermore, contact angle measurements were carried out. The sign and magnitude of the thermodynamic parameters indicated spontaneity of solubilization process. The phase solubility studies revealed A(L) type of curves for the carriers. Unlike traditional solid dispersion systems, the crystal form of drug in the formulated systems could not be converted to amorphous form. Most of the studied grades showed dissolution improvement vis-à-vis pure drug, with Pluronic F-127 as the most promising carrier. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model. Thus, the results demonstrated that tadalafil/Pluronic F-127 solid dispersion system is a direct and feasible technology which represents a potential candidate for delivering a poorly water-soluble drug with enhanced solubility and dissolution.

Tadalafil Inclusion in Microporous Silica as Effective Dissolution Enhancer: Optimization of Loading Procedure and Molecular State Characterization

Tadalafil is an efficient drug used to treat erectile dysfunction characterized by poor water solubility, which has a negative influence on its bioavailability. Utilization of microporous silica represents an effective and facile technology to increase the dissolution rate of poorly soluble drugs. Our strategy involved directly introducing tadalafil as guest molecule into microporous silica as host material by incipient wetness impregnation method. To optimize tadalafil inclusion, response surface methodology (RSM) using 3(3) factorial design was utilized. Furthermore, to investigate the molecular state of tadalafil, Fourier-transform infrared spectroscopy, differential scanning calorimetery, thermal gravimetrical analysis, nitrogen adsorption, and powder X-ray diffraction (PXRD) were carried out. The results obtained pointed out that the quantity of microporous silica was the predominant factor that increased the loading efficiency. For the optimized formula, the loading efficiency was 42.50 wt %. Adsorption-desorption experiments indicated that tadalafil has been introduced into the micropores. Powder XRD and differential scanning calorimetry analyses revealed that tadalafil is arranged in amorphous form. In addition, the dissolution rate of tadalafil from the microporous silica was faster than that of free drug. Amorphous tadalafil occluded in microporous silica did not crystallize over 3 months. These findings contributed in opening a new strategy concerning the utilization of porous silica for the dissolution rate enhancement.

Tensile strength of some pharmaceutical compacts and their relation to surface free energy

Abstract The time-dependent nature of plastic flow, of 7 pharmaceutical powders, and its effect on the tensile strength of their compacts after consolidation is reported. Magnesium stearate compact showed no change in strength with time. For plastic materials a In-In plot of tensile strength versus time resulted in a straight line. The obtained visco-elastic slope, v, is a measure of plasticity. The more pronounced the plastic flow the greater the slope. After 30 min from compaction, the values of tensile strength obtained were correlated quantitatively to the surface free energy of the materials studied. High surface free energies were associated with higher tensile strength. A constant, k, which relates the surface free energy of materials to the tensile strength of compacts is defined. Plastic materials exhibit the same k value which was greater than that obtained for magnesium stearate.

Ciprofloxacin Liposomes as Vesicular Reservoirs for Ocular Delivery: Formulation, Optimization, and In Vitro Characterization

Management of extraocular diseases is mainly limited by the inability to provide long-term drug delivery without avoiding the systemic drug exposure and/or affecting the intraocular structures and poor availability of drugs, which may be overcome by prolonging the contact time with the ocular system, for instance with liposomes. Development and optimization of reverse phase evaporation ciprofloxacin (CPF) HCl liposomes for ocular drug delivery was carried out using a 25 full factorial design based on five independent variables. The effects of the studied parameters on drug entrapment efficiency (EE), particle size, and percentage of drug released after 1 and 10 h were investigated. The results obtained pointed out that the molar concentration of cholesterol was the predominant factor that increased the EE% of the drug and the particle size responses. The percentage of drug released after 1 h was significantly controlled by the initial CPF concentration while that after 10 h was controlled by molar cholesterol concentration. The designed liposomes had average particle sizes that ranged from 2.5 to 7.23 μm. In addition, liposomes revealed a fast release during the first hour followed by a more gradual drug release during the 24-h period according to Higuchi diffusion model.

Micellar properties of non-ionic surfactants in relation to their solubility parameters

Abstract The solubility parameters of various polyoxyethylated non-ionic surfactants were calculated according to 3 different methods: by Fedors approach; from molar attraction constants; by including a hydrogen-bonding component to account for hydration. The computed solubility parameters for the surfactants were then correlated with their critical micelle concentrations (CMC). The relationships included 3 homologous surfactant series based on polyoxyethylated ethers, octyl- and nonyl-phenols, and fatty acid esters of sorbitan. The total solubility parameters, δ0, corrected for hydrogen bonding increased linearly with increasing the CMC. The resulting linear relationships permit the prediction of the CMC of any surfactant within a homologous series from any of its calculated solubility parameters. Branching of decaoxyethylated octylphenol to give t-octylphenol decreased the CMC by a factor of 1.3, and increased δ0 by 0.31 (cal/ml) 1 2 . The presence of double bond in TWEEN 80 decreased the CMC by a factor of 2, and increased δ0 by only 0.03 (cal/ml) 1 2 . A greater double bond effect on solubility parameter of ~1.0 (cal/ml) 1 2 was noticed in the case of long-chain polyoxyethylated ethers than in TWEENs. The double bond contribution to CMC and to the total solubility parameter is not additive for the different homologous series and varies with the surfactant structure. The solubility parameter concept was also applied to analyse some solubilization data.

Solubilization of Carbamazepin by Different Classes of Nonionic Surfactants and a Bile Salt

AbstractSolubilization of carbamazepin, a slightly soluble antiepileptic drug is investigated in representative classes of eight nonionic surfactants, viz., Tweens 20, 40, 60 & 80; Myrjs 51 & 52; and Brijs 35 & 98. The solubility of carbamazepin in acueous solutions of these detergents was determined over the concentration range of 0-0.09 mole/liter at 37°. A marked increase in solubility is noticed with all the surfactants used. Dihydroxy bile salts such as sodium deoxycholate have many detergent-like properties derived from their unusual amphiphilic structure. The solubility of carbamazepin in sodium deoxycholate was determined over the concentration range of 0-0.2 mole/liter at 37°. Increasing the concentration of the bile salt, increased the solubilized amount of carbamazepin. Comparison with solubilisation in typical micelle-forming systems indicates that the self-association of the bile salt is very complex and exhibit a very different pattern. Further examination of the solubilization data in terms...

Crystallization of Progesterone for Pulmonary Drug Delivery

The purpose of this study is to investigate the suitability of the crystallization process to produce microcrystals of progesterone for respiratory drug delivery. Crystallization of progesterone was carried out from water-isopropanol (IPA) mixture. The antisolvent (water) was added at two different addition rates (10 and 100 mL/min). The mass percentage of antisolvent was varied between (50% and 75%), and the initial drug concentration was adjusted at (0.5 and 1 g/L). The effect of crystallization method (antisolvent precipitation or combined cooling and antisolvent) was also examined. These operating conditions were investigated in a 2(4) factorial design in an effort to optimize the process. Different solid-state and surface characterization techniques were applied in conjunction with measurements of powder flow properties using aerodynamic particle sizer (APS). Powder dispersibility and aerosol performance were analyzed using Anderson Cascade Impactor (ACI). Antisolvent addition rate, initial drug concentration and dynamic solvent composition are shown to have a significant effect on the aerosol characteristics of progesterone microcrystals. An increase of 38.73% in the fine particle fraction (FPF) was demonstrated for some powders produced by combined cooling and antisolvent crystallization. In conclusion, it was possible to control particle size and hence, pulmonary deposition using process parameters alone, and produce particles with a narrow particle size distribution and a mean particle size of 5 microm with nearly no particles larger than 10 microm by direct crystallization. The suitability of deep pulmonary deposition was proved by the platelet-like morphology of processed microcrystals and greater surface-to-volume ratio than spherical particles.

Nanovesicular carrier-mediated transdermal delivery of tadalafil: i-formulation and physicsochemical characterization.

Abstract The limited permeability of stratum corneum, the main skin barrier, towards pharmaceutical active ingredients represents the main obstacle encounter the transdermal drug delivery system. In the current study, penetration enhancer-containing nanoliposomes, that is, penetrosomes were formulated incorporating tadalafil to enhance its transdermal permeability. Hydration-sonication method was used to prepared penetrosomes bearing tadalafil. The prepared nanocarriers were characterized in terms of vesicles shape and surface morphology, size and size distribution, zeta potential, entrapment efficiency, and elasticity. Results pointed to that penetrosomes were spherical in shape with a unilamellar-closed structure in the nanometric narrow size range proved by their law span index. Penetrosomes formulations elaborated deformable vesicles more than the conventional liposomes, with the Penetrosomes-based Labrasol® being the most deformable formulation. Penetrosomes-ultraelastic nanoliposomes represent an attractive vehicle for transdermal delivery of tadalafil to treat erectile dysfunction.

Relationship Between the Solubility Parameter and the Surface Free Energy of Some Solids

AbstractSolubility parameters for a number of drugs and related organic solids were determined from their dispersion and polar surface free energy data by means of an equation found to be valid for solvents. The relation fits quite well all solids investigated with an excellent correlation coefficient. The calculated solubility parameters, O, were checked with the ones estimated from molecular groups and fragment constants according to Fedors method, F. A similar O of 14.6 was obtained for o-hydroxybenzoic and p-hgdroxybensoic acids. The deviations from F shown in ethyl-p-aminobenzoate, benzoic acid, and aspirin were attributed to the imperfection of their vapor.The solubility profile of hydrocortisone acetate was obtained in dioxane-water mixtures, and the solubility parameter of the drug was determined from the peak solubility in this binary solvent system. The experimental results for some drugs were compared with their solubility parameters calculated from the surface free energy data. Excellent agree...

The effect of film-inducing substances on the characteristics of binary powder mixtures

Abstract Compaction of a brittle material, phenacetin, could be improved by proper choice of the diluent and film-inducing agent. Aspirin, potassium chloride and sodium chloride were used owing to their ability to relieve stresses by plastic flow. The effect of Aerosil, Eudragit-E and magnesium stearate on the characteristics of these binary mixtures as well as their mechanism were presented. In almost all Systems the results of the repose angle and bulk density were consistent with those obtained from tensile strength measurement. Phenacetin tablets needed higher ratios of potassium chloride or sodium chloride to produce satisfactory compacts than in the case of aspirin. A linear relation was obtained by plotting log packing fraction of various potassium chloride to phenacetin binary mixtures versus log tensile strength. At a given pressure the tensile strength of phenacetin alone could be estimated.