Objective: The objective of this study is to develop and characterize in situ thermosensitive gels for the vaginal administration of sildenafil as a potential treatment of endometrial thinning occurring as a result of using clomiphene citrate for ovulation induction in women with type II eugonadotrophic anovulation. While sildenafil has shown promising results in the treatment of infertility in women, the lack of vaginal pharmaceutical preparation and the side effects associated with oral sildenafil limit its clinical effectiveness. Methods: Sildenafil citrate in situ forming gels were prepared using different grades of PluronicVR (PF-68 and PF-127). Mucoadhesive polymers as sodium alginate and hydroxyethyl cellulose were added to the gels in different concentrations and the effect on gel properties was studied. The formulations were evaluated in terms of viscosity, gelation temperature (Tsol-gel), mucoadhesion properties, and in vitro drug release characteristics. Selected formulations were evaluated in women with clomiphene citrate failure due to thin endometrium (Clinicaltrial.gov identifier NCT02766725). Results: The Tsol-gel decreased with increasing PF-127 concentration and it was modulated by addition of PF-68 to be within the acceptable range of 28–37 _C. Increasing PluronicVR concentration increased gel viscosity and mucoadhesive force but decreased drug release rate. Clinical results showed that the in situ sildenafil vaginal gel significantly increased endometrial thickness and uterine blood flow with no reported side effects. Further, these results were achieved at lower frequency and duration of drug administration. Conclusion: Sildenafil thermosensitive vaginal gels might result in improved potential of pregnancy in anovulatory patients with clomiphene citrate failure due to thin endometrium.

Glibenclamide (GLC) is a potent oral hypoglycemic drug widely-used in the treatment of type II diabetes mellitus. It is practically-insoluble in water which hindering its dissolution at the gastric pH hence, lowering its absorption and oral bioavailability (45% only. The aim of this work was to improve such dissolution via formulation of adsorbates and co-adsorbates to enhance the oral bioavailability of GLC. This will enable its use at a lower dose to minimize the cost and possible side effects. Adsorption of drug onto different adsorbents including Laponite RD, Laponite FP, Neusilin US2, Aerosil 200 and Florite R was studied and Langmuir adsorption isotherms were constructed. Moreover, the effect of surfactant addition on the adsorption process was studied also using different concentrations of different surfactants namely; Tween 80, Pluronic F-127 and Pluronic F-68. Laponite RD as an adsorbent and Pluronic F-68 as a surfactant showed the best results and therefore, they were used in the formulation of adsorbates and co-adsorbates. Adsorbates of drug with Laponite RD were prepared in different weight ratios using two different techniques; physical mixing and solvent evaporation technique. Co-adsorbates of drug with pluronic F-68 and Laponite RD were prepared in different weight ratios by solvent evaporation technique. The prepared systems were tested for their drug content and in-vitro dissolution rate. The results showed marked enhancement of GLC in-vitro dissolution rate compared with untreated GLC which would be promising in further incorporation of the optimized formulation into several dosage forms with enhanced bioavailability.

Glibenclamide (GLC) is a potent oral hypoglycemic drug widely-used in the treatment of type II diabetes mellitus. It is practically-insoluble in water which hindering its dissolution at the gastric pH hence, lowering its absorption and oral bioavailability (45% only. The aim of this work was to improve such dissolution via formulation of adsorbates and co-adsorbates to enhance the oral bioavailability of GLC. This will enable its use at a lower dose to minimize the cost and possible side effects. Adsorption of drug onto different adsorbents including Laponite RD, Laponite FP, Neusilin US2, Aerosil 200 and Florite R was studied and Langmuir adsorption isotherms were constructed. Moreover, the effect of surfactant addition on the adsorption process was studied also using different concentrations of different surfactants namely; Tween 80, Pluronic F-127 and Pluronic F-68. Laponite RD as an adsorbent and Pluronic F-68 as a surfactant showed the best results and therefore, they were used in the formulation of adsorbates and co-adsorbates. Adsorbates of drug with Laponite RD were prepared in different weight ratios using two different techniques; physical mixing and solvent evaporation technique. Co-adsorbates of drug with pluronic F-68 and Laponite RD were prepared in different weight ratios by solvent evaporation technique. The prepared systems were tested for their drug content and in-vitro dissolution rate. The results showed marked enhancement of GLC in-vitro dissolution rate compared with untreated GLC which would be promising in further incorporation of the optimized formulation into several dosage forms with enhanced bioavailability.

The use of nanoparticles for drug delivery is still restricted by their limited stability when stored in an aqueous medium. Freeze drying is the standard method for long-term storage of colloidal nanoparticles; however the method needs to be elaborated for each formulation. Spray freeze drying (SFD) is proposed here as a promising alternative for lyophilizing colloidal nanoparticles. Different types of polymeric and lipid nanoparticles were prepared and characterized. Afterwards, samples were spray freeze dried by spraying into a column of cold air with a constant concentration of different cryoprotectants, and the frozen spherules were collected for further freeze drying. Similar samples were prepared using the commonly used technique, freeze drying, as controls. Using SFD, fast-dissolving, spherical and porous nanocomposite microparticles with remarkably high flowability (CI ≤ 10) were produced. On the contrary to similar samples prepared using the freeze drying technique, the investigated polymeric and lipid nanoparticles were completely reconstituted (Sf/Si ratio 1.5) after SFD. SFD proved to be an effective platform for improving the long-term stability of colloidal nanoparticles.

Lung cancer, the deadliest solid tumor among all types of cancer, remains difficult to treat. This is a result of unavoidable exposure to carcinogens, poor diagnosis, the lack of targeted drug delivery platforms and limitations associated with delivery of drug to deep lung tissues. Development of a non-invasive, patient-convenient formula for the targeted delivery of chemotherapeutics to cancer in deep lung tissue is the aim of this study. The formulation consisted of inhalable polyvinylpyrrolidone (PVP)/maltodextrin (MD)-based microparticles (MPs) encapsulating chitosan (CS) nanoparticles (NPs) loaded with either drug only or drug and magnetic nanoparticles (MNPs). Drug release from CS NPs was enhanced with the aid of MNPs by a factor of 1.7 in response to external magnetic field. Preferential toxicity by CS NPs was shown towards tumor cells (A549) in comparison to cultured fibroblasts (L929). The prepared spray freeze dried (SFD) powders for CS NPs and CS MNPs were of the same size at ∼6 μm. They had a fine particle fraction (FPF≤5.2 μm) of 40–42% w/w and mass median aerodynamic diameter (MMAD) of 5–6 μm as determined by the Next Generation Impactor (NGI). SFD-MPs of CS MNPs possess higher MMAD due to the high density associated with encapsulated MNPs. The developed formulation demonstrates several capabilities including tissue targeting, controlled drug release, and the possible imaging and diagnostic values (due to its MNPs content) and therefore represents an improved therapeutic platform for drug delivery to cancer in deep lung tissue.

The effect of adding transition metals to the electrolyte containing proton pump inhibitors, such as rabeprazole sodium (RAB sodium), on the voltammetric response of pencil graphite electrode was studied. Both square-wave adsorptive stripping voltammetry (SWAdSV) and cyclic voltammetry (CV) were utilized to elucidate and confirm the possible complexation reaction that could occur between RAB sodium and cobalt as a transition metal. The current signal due to the oxidation process was a function of the concentration of RAB sodium, pH of the medium, cobalt concentration, scan rate, frequency, and deposition time at the electrode surface. This phenomenon could be used for the determination of RAB sodium using CV and SWAdSV. The oxidation peak current linearly varied with the concentration over the range of 0.05–9
109 M and 0.2–8.5
107 M for SWAdSV and CV, respectively. The limits of detection were found to be 0.015
109 M and 0.06
107 M for SWAdSV and CV, respectively. The validity of using these methods for the determination of RAB sodium in its pharmaceutical formulation and human urine samples was evaluated.

The effect of adding transition metals to the electrolyte containing proton pump inhibitors, such as rabeprazole sodium (RAB sodium), on the voltammetric response of pencil graphite electrode was studied. Both square-wave adsorptive stripping voltammetry (SWAdSV) and cyclic voltammetry (CV) were utilized to elucidate and confirm the possible complexation reaction that could occur between RAB sodium and cobalt as a transition metal. The current signal due to the oxidation process was a function of the concentration of RAB sodium, pH of the medium, cobalt concentration, scan rate, frequency, and deposition time at the electrode surface. This phenomenon could be used for the determination of RAB sodium using CV and SWAdSV. The oxidation peak current linearly varied with the concentration over the range of 0.05–9
109 M and 0.2–8.5
107 M for SWAdSV and CV, respectively. The limits of detection were found to be 0.015
109 M and 0.06
107 M for SWAdSV and CV, respectively. The validity of using these methods for the determination of RAB sodium in its pharmaceutical formulation and human urine samples was evaluated.

The effect of adding transition metals to the electrolyte containing proton pump inhibitors, such as rabeprazole sodium (RAB sodium), on the voltammetric response of pencil graphite electrode was studied. Both square-wave adsorptive stripping voltammetry (SWAdSV) and cyclic voltammetry (CV) were utilized to elucidate and confirm the possible complexation reaction that could occur between RAB sodium and cobalt as a transition metal. The current signal due to the oxidation process was a function of the concentration of RAB sodium, pH of the medium, cobalt concentration, scan rate, frequency, and deposition time at the electrode surface. This phenomenon could be used for the determination of RAB sodium using CV and SWAdSV. The oxidation peak current linearly varied with the concentration over the range of 0.05–9
109 M and 0.2–8.5
107 M for SWAdSV and CV, respectively. The limits of detection were found to be 0.015
109 M and 0.06
107 M for SWAdSV and CV, respectively. The validity of using these methods for the determination of RAB sodium in its pharmaceutical formulation and human urine samples was evaluated.

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Stereoselective biocatalysis by crotonase superfamily enzymes is exemplified by use of engineered 5-carboxymethylproline synthases (CMPSs) for preparation of functionalized 5-carboxymethylproline (5-CMP) derivatives methylated at two positions (i.e. C2/C6, C3/C6 and C5/C6), including products with a quaternary centre, from appropriately-substituted-amino acid aldehydes and C-2 epimeric methylmalonyl-CoA. The enzymatically-produced disubstituted 5-CMPs were converted by carbapenam synthetase into methylated bicyclic Β-lactams, which manifest improved hydrolytic stability compared to the unsubstituted carbapenams. The results highlight the use of modi-fied carbapenem biosynthesis enzymes for production of new carbapenams with improved properties.