The colon is a promising target for drug delivery owing to its long transit time of up to 78 h, which is likely to increase the time available for drug absorption. Progesterone has a short elimination half-life and undergoes extensive first-pass metabolism, which results in very low oral bioavailability ($25%). To overcome these shortcomings, we developed an oral multiparticulate system for the colonic delivery of progesterone. Zn-pectinate/chitosan microparticles were prepared by ionotropic gelation and characterized for their size, shape, weight, drug entrapment efficiency, mucoadhesion and swelling behavior. The effect of crosslinking pH, cross-linking time and chitosan concentration on progesterone release were also studied. Spherical microparticles having a diameter of 580-720 mm were obtained. Drug entrapment efficiency of $75-100% was obtained depending on the microparticle composition. Microparticle mucoadhesive properties were dependent on the pectin concentration, as well as the cross-linking pH. Progesterone release in simulated gastric fluids was minimal (3-9%), followed by burst release at pH 6.8 and a sustained phase at pH 7.4. The in vivo study revealed that the microparticles significantly increased progesterone residence time in the plasma and increased its relative bioavailability to $168%, compared to the drug alone. This study confirms the potential of Zn-pectinate/chitosan microparticles as a colon-specific drug delivery system able to enhance the oral bioavailability of progesterone or similar drugs.

Slow-release buccal bioadhesive tablets of miconazole nitrate were prepared by using polymer mixtures of buccoadhesive materials such as hydroxypropylmethylcellulose, sodium carboxymethylcellulose, carbopol 934p, and sodium alginate. The physicochemical properties, swelling index, microenvironment pH, in vitro drug release, in vivo buccoadhesion time, and miconazole salivary concentrations of the prepared tablets were shown to be dependent on the type and composition of the buccoadhesive materials used. The dissolution of miconazole from all the prepared tablets into phosphate buffer (pH 6.8) was controlled and followed non-Fickian release mechanisms. All the prepared tablets gave reasonable buccoadhesion time (2.45-3.65 hr). Infrared spectroscopy and differential scan calorimetry studies revealed the absence of significant interactions between miconazole nitrate and the selected buccoadhesive materials. Duration of the antifungal activity as measured by the inhibition zone of Candida albicans by extracted human saliva was significantly longer (p < 0.05), compared with commercial miconazole oral gel (Daktaren oral gel). Based on the results obtained, the prepared slow-release buccoadhesive tablets of miconazole would markedly prolong the duration of the antifungal activity with more patient convenience.

Topical gel formulations of diclofenac sodium were prepared by using sodium carboxymethylcellulose (NaCMC), a low-toxicity cellulose polymer as a gel-forming material that is biocompatible and biodegradable. The influence of various formulation variables, such as initial drug concentrations and NaCMC concentration, and certain skin permeation enhancers on release characteristics of the diclofenac sodium from the prepared gels through a standard cellophane membrane was studied in comparison with four commercially available gel formulations of diclofenac sodium,. The cumulative amounts released and the apparent release rates were higher for the prepared gels in comparison with the commercial formulations. Skin permeation studies using abdominal rat skin revealed good improvement of skin permeation characteristics of diclofenac sodium using NaCMC gels as compared to the commercial gels. The cumulative amount permeated at 6 h (microg/cm2), steady-state flux Jss (microg/cm2 h), lag time tL (h), permeability coefficient kp (cm/s), partition coefficient k, and diffusion coefficient D (cm2/s) were determined for the prepared gels in comparison with the commercial gels. Skin permeation enhancers such as isopropyl alcohol (IPA), Tween 80, and alpha-tocopherol polyethylene glycol succinate (TPGS) exhibited little or no effect on the permeation characteristics of diclofenac sodium. Infrared (IR) spectrum and differential scanning calorimetry (DSC) studies on the pure diclofenac sodium, NaCMC, and their physical mixture at a 1:1 ratio revealed that there was no positive evidence for the interactions between the drug and NaCMC, indicating the compatibility of the drug and the vehicle. Based on experimental results, preparation of diclofenac sodium gels using NaCMC vehicle is promising.

In this paper, we study the time evolution of the entropies and the degree of entanglement in the mixed state for a multi-quanta JC model taking into consideration Stark shift and Kerr-like medium effect, we use a numerical method to investigate the time evolution of the partial entropy of the atom and field subsystem. This is done in the framework of the multi-quanta presses JC model with both the Stark shift and Kerr-like medium effect added. Furthermore, we examine the effect of the superposition states and a statistical mixture of coherent states as an initial field on the entropies and entanglement. Our results show that the setting of the initial state play an important role in the evolution of the sub-entropies and entanglement. KEY WORDS: entropies; the degree of entanglement; mixed state; the superposition states and a statistical mixture of coherent states.

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This paper reports, for the first time, the data on the pharmacokinetic characteristics of diclofenac sodium and cefadroxil at Albaha, 2500 M altitude (ALT) , KSA. Therefore, the objective of this study was to compare the plasma concentrations and pharmacokinetic parameters of diclofenac sodium (Voltaren  50 tablets, Ciba Geigy, USA) and cefadroxil (Ultrcef  500 capsules, Bristol L. Germany) at altitude of 2500 M (ALT) and at sea level (SEA) after oral administration to 12 healthy volunteers. A two-way cross over study design was used to compare pharmacokinetic parameters at ALT and SEA. Following drug administration, blood withdrawn into heparinized test tubes over a period of 12 hours. Drug concentrations were determined in the withdrawn samples by fully validated and optimized HPLC methods for the two drugs. The pharmacokinetic parameters including C max , t max , t 0.5e , t 0.5a , K e , K a , V d , Cl T , AUC 0-12h , and AUC 0-∞ were determined by a computer programs. Statistical analysis of the obtained plasma drug concentrations and pharmacokinetic parameters were performed using ANOVA computerized system. Results obtained showed significant differences in the plasma concentrations and all pharmacokinetic parameters of the two drugs at ALT as compared to SEA. There was a significant increase in C max and AUC 0-12h , of both drugs at ALT as compared to SEA. The values of Vd and Cl T were significantly lower at ALT than SEA. ALT could markedly inhibit the metabolism and renal excretion of both drugs as indicated by significant increase in the elimination half-lives (t 0.5e ) and decrease in the elimination rate constant (K e ) at ALT as compared to SEA. The obtained results clearly indicate that the plasma concentrations and all the pharmacokinetic parameters of both diclofenac sodium and cefadroxil are significantly modified by ALT. Therefore, dosage regiemens adjustment is important when diclofenac sodium and cefadroxil are prescribed for administration at ALT to maintain drug efficacy and safety and to avoid drug , s toxicity.

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