Viviane F. Naggar

Preparation and evaluation of ketoprofen floating oral delivery system

A sustained release system for ketoprofen designed to increase its residence time in the stomach without contact with the mucosa was achieved through the preparation of floating microparticles by the emulsion-solvent diffusion technique. Four different ratios of Eudragit S100 (ES) with Eudragit RL (ERL) were used to form the floating microparticles. The drug retained in the floating microparticles decreased with increase in ERL content. All floating microparticle formulations showed good flow properties and packability. Scanning electron microscopy and particle size analysis revealed differences between the formulations as to their appearance and size distribution. X-ray and DSC examination showed the amorphous nature of the drug. Release rates were generally low in 0.1 N HCl especially in presence of high content of ES while in phosphate buffer pH 6.8, high amounts of ES tended to give a higher release rate. Floating ability in 0.1 N HCl, 0.1 N HCl containing 0.02% Tween 20 and simulated gastric fluid without pepsin was also tested. The formulation containing ES:ERL1:1 (FIII) exhibited high percentage of floating particles in all examined media.

Chitosan and sodium alginate—Based bioadhesive vaginal tablets

Metronidazole was formulated in mucoadhesive vaginal tablets by directly compressing the natural cationic polymer chitosan, loosely cross-linked with glutaraldehyde, together with sodium alginate with or ine cellulose (MCC). Sodium carboxymethylcellulose (CMC) was added to some of the formulations. The drug content in tablets was 20%. Drug dissolution rate studies from tablets were carried out in buffer pH 4.8 and distilled water. Swelling indices and adhesion forces were also measured for all formulations. The formula (FIII) containing 6% chitosan, 24% sodium alginate, 30% sodium CMC, and 20% MCC showed adequate release properties in both media and gave lower values of swelling index compared with the other examined formulations. FIII also proved to have good adhesion properties with minimum applied weights. Moreover, its release properties (% dissolution efficiency, DE) in buffer pH 4.8, as well as release mechanism (n values), were negligibly affected by aging. Thus, this formula may be considered a good candidate for vaginal mucoadhesive dosage forms.

PG‐liposomes: novel lipid vesicles for skin delivery of drugs

A novel type of lipid vesicles, propylene glycol‐embodying liposomes or PG‐liposomes, composed of phospholipid, propylene glycol and water, is introduced. The new lipid vesicles were developed and investigated as carriers for skin delivery of the model drug, cinchocaine base. PG‐liposomes showed high entrapment efficiency and were stable for at least one month of storage at 5 ± 1 °C. Preliminary in‐vivo skin deposition studies, carried out using albino rabbit dorsal skin, showed that PG‐liposomes were superior to traditional liposomes, deformable liposomes and ethosomes, suggesting that PG‐liposomes, introduced in the current work, are promising carriers for skin delivery of drugs.

Optimization of acyclovir oral tablets based on gastroretention technology: Factorial design analysis and physicochemical characterization studies

The purpose of this research was to prepare a floating drug delivery system of acyclovir. Floating matrix tablets of acyclovir were developed to prolong gastric residence time and increase its bioavailability. The tablets were prepared by direct compression technique, using polymers such as hydroxypropylmethylcellulose 4000, Compritol 888. Sodium bicarbonate was used as a gas-generating agent. A 32 factorial design using the Design Expert Software (version 7.1.6) was applied to optimize the drug release profile systematically. The amounts of hydroxypropylmethylcellulose 4000 (X1) and Compritol 888 (X2) were selected as independent variables and the percentage drug released in 1 (Q1), 6 (Q6), and 12 (Q12) h as dependent variables. The results of factorial design indicated that a high level of both hydroxypropylmethylcellulose 4000 (X1) and Compritol 888 (X2) favors the preparation of floating controlled-release of acyclovir tablets. Also, a good correlation was observed between predicted and actual values of the dependent variables chosen for the study. By fitting the data into zero-order, first-order, and Higuchi models, we concluded that the release followed Higuchi diffusion kinetics. Storage of the prepared formulations at 40°C/75% relative humidity for 3 months showed no significant change in drug release profiles and buoyancy of the floating tablets. We can conclude that a combination of hydroxypropylmethylcellulose 4000, Compritol 888, and sodium bicarbonate can be used to increase the gastric residence time of the dosage form up to 12 h. These floating tablets seem to be a promising gastroretentive drug delivery system.

Thermodynamics of paracetamol solubility in sugar-water cosolvent systems

Abstract The solubility of paracetamol in different concentrations of sorbitol, glucose and sucrose solutions was studied at 20 and 37°C. There was an appreciable decrease in solubility of the drug at both temperatures, the effect generally being more apparent at the lower temperature as reflected by the solubility ratios. Sorbitol exhibited the greatest effect followed by glucose then sucrose. Thermodynamic parameters were calculated and showed the nonspontaneity of the solubility process (positive free energy values). Entropy changes were positive or of small negative values, while enthalpy changes were positive and of relatively small values. Such results are compatible with the occurrence of hydrophobic interactions that led to a reduction in the solubility of the antipyretic agent. However, the effect of sugar concentration on the thermodynamic parameters was not the same with the three sugars tested, suggesting differences in their solvency characteristics.

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.

Effect of magnesium trisilicate on nitrofurantoin absorption.

In vitro adsorption studies revealed that for an identical initial concentration of nitrofurantoin, magnesium trisilicate exhibited the greatest adsorptive capacity with bismuth oxycarbonate, talc, kaolin, and magnesium oxide exhibiting intermediate adsorptive powers, while aluminum hydroxide and calcium carbonate exhibited low or no adsorption properties. Trials to elute the drug with acidic or alkaline solution were unsuccessful. The in vivo absorption characteristics of nitrofurantoin and nitrofurantoin‐magnesium trisilicate combination were evaluated in 6 healthy males. Administration of magnesium trisilicate with nitrofurantoin reduced the rate and extent of its excretion reflecting decrease in both rate and extent of absorption. The time during which the drug concentration in the urine was above the minimum effective concentration of 32 µg/ml was also significantly reduced after administration of the antacid.

Preparation and evaluation of periodontal films based on polyelectrolyte complex formation.

Abstract Local intra-pocket drug delivery devices can provide an effective concentration of the antimicrobial agent at the site of action with avoidance of undesirable side effects. This study explored the application of chitosan-alginate and chitosan-pectin polyelectrolyte complex (PEC) films as drug release regulators for tetracycline HCl (Tc) to treat periodontal pockets. Periodontal films with 1:1 Tc:PEC ratio were prepared using 1:1 chitosan (Ch) to sodium alginate (A) or 1:3 Ch to pectin (P). The scanning electron microscope showed acceptable film appearance and differential scanning calorimetry analysis confirmed complex formation. The in vitro release studies for both films showed a burst drug release, followed by prolonged release for 70 h. A prolonged antibacterial activity of both films against Staphylococcus aureus ATCC 6538 was observed over a period of 21 days. Aging studies indicated that the five months storage period in freezer did not significantly influence the drug release profile or the antibacterial activity of both films. Clinical evaluation showed a significant reduction in pocket depth (p < 0.0001) to their normal values (≤3 mm). PEC films could be exploited as a prolonged drug release devices for treatment of periodontal pockets.

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...

Formulation and physicochemical characterization of chitosan/acyclovir co-crystals.

In the current study, the influence of chitosan on the dissolution rate and bioavailability of acyclovir has been illustrated through the preparation of co-crystals by simple solvent change method. Chitosan was precipitated on acyclovir crystals using sodium citrate as the salting out agent. The pure drug and the prepared co-crystals using different concentrations and molecular weights of chitosan were characterized in terms of drug content, particle size, thermal behavior, IR analysis, surface morphology, in vitro drug release and physical stability. The results obtained showed that the practical yield of the prepared co-crystals was found to be inversely proportional to chitosan concentration. The drug content of the co-crystals was uniform among the different batches. The prepared co-crystals showed a slower drug release when compared to that of pure drug. The considerable change in the dissolution rate of acyclovir from optimized crystal formulation was attributed to the wetting effect of chitosan, the reduction in drug crystallinity and the altered surface morphology. The thermograms showed a decrease in the melting enthalpy of acyclovir indicating a disorder in the crystalline content whereas IR spectroscopy studies revealed an interaction between acyclovir and chitosan. The optimized co-crystals were stable for three months at 40°C and 75 ± 5% RH.