Cocrystals have gained a lot of consideration regarding its superior role in enhancement of solubility and dissolution of the included API. Cocrystals could be converted to coamorphous systems via different techniques like milling and quench cooling; however, the use of spray-drying technique has not been investigated before. So, the aim of this study was to explore the effect of spray drying on the amorphization of indomethacin/nicotinamide, INDNIC, as model cocrystals. Spray-drying operating parameters were optimized using the Taguchi design of experiment for maximum powder yield and low moisture content. The obtained INDNIC spray-dried cocrystals were characterized for their degree of crystallinity, morphology, moisture content, and dissolution performance. In addition, stability study was performed at different temperature and humidity conditions. Experimental design results delineate that spray-drying inlet temperature and cocrystal concentrations as the most influential factors for maximum powder yield and low moisture content. Powder X-ray diffraction and differential scanning calorimetry studies revealed the conversion of INDNIC cocrystals to a partial coamorphous or coamorphous structure without dissociation of INDNIC molecular structure. INDNIC coamorphous powders showed a significantly higher release of IND compared with cocrystals and remain physically stable for 2 months when stored in the refrigerator.

Background Leukaemia is the most prevalent form of cancer-causing death in a large number of populations and needs prompt and effective treatment. Chemotherapeutics can be used to treat leukaemia, but their pronounced killing effects to other living cells is still an issue. Active targeting to certain specific receptors in leukaemic cells is the best way to avoid damage to other living cells. Leukaemic cells can be targeted using novel nanoparticles (NPs) coated with a specific ligand, such as octreotide (OCD), to target somatostatin receptor type 2 (SSTR2), which is expressed in leukaemic cells. Methods Amino-PEGylated quantum dots (QDs) were chosen as model NPs. The QDs were first succinylated using succinic anhydride and then coated with OCD. The reactivity and selectivity of the formulated QDs-OCD were studied in cell lines with well-expressed SSTR2, while fluorescence was detected using confocal laser scanning microscopy (CLSM) and flow cytometry (FACS). Conclusively, QD-OCD targeting to blood cells was studied in vivo in mice and detected using inductively coupled plasma mass spectrometry and CLSM in tissues. Results Highly stable QDs coated with OCD were prepared. FACS and CLSM showed highly definite interactions with overexpressed SSTR2 in the investigated cell lines. Moreover, the in vivo results revealed a higher concentration of QDs-OCD in blood cells. The fluorescence intensity of the QDs-OCD was highly accumulated in blood cells, while the unmodified QDs did not accumulate significantly in blood cells. Conclusion: The formulated novel QDs-OCD can target SSTR2 overexpressed in blood cells with great potential for treating blood cancer.

Sulpiride (SUL) is a dopamine D2-receptor antagonist used for management of GIT disturbance and it has anti-psychotic activities based on the administered dose. SUL undergoes P-glycoprotein eux, which lead to poor bioavailability and erratic absorption. Therefore, the objective of this research was an attempt to enhance the oral bioavailability of SUL via formulation of fast disintegrating tablets (SUL-FDTs) with a rapid onset of action. A32 full-factorial design was performed for optimization of SUL-FDTs using desirability function. The concentration of superdisintegrant (X1) and Prosolv® (X2) were selected as independent formulation variables for the preparation and optimization of SUL-FDTs using direct compression technique. The prepared SUL-FDTs were investigated regarding their mechanical strength, disintegration time, drug release and in vivo pharmacokinetic analysis in rabbits. The optimized formulation has hardness of 4.58  0.52 KP, friability of 0.73  0.158%, disintegration time of 37.5  1.87 s and drug release of 100.51  1.34% after 30 min. In addition, the optimized SUL-FDTs showed a significant (p 0.01) increase in Cmax and AUC(0–1) and a relative bioavailability of about 9.3 fold compared to the commercial product. It could be concluded that SUL-FDTs are a promising formulation for enhancing the oral bioavailability of SUL concomitant with a fast action.

This study was designed to evaluate suitability of chitosan polymer as a vehicle for topical delivery system. Quercetin (QUT) is a natural flavonoid, was incorporated into the gel vehicles in a concentration of 0.5% w/v. Gels were prepared with three different concentrations and different molecular weights of chitosan. Viscosity, drug release from prepared gels, permeation of drug through skin rat and anti-inflammatory activity of the drug using carrageenan induced rat paw edema method were studied. In-vitro release characteristics of the drug from different gels were carried out using dialysis membrane in phosphate buffer, pH 5.5. The release data were treated with various kinetic principles to assess the relevant parameters. The general rank order of QUT release was F1 > F4 > F2 > F3 > F5. The results also showed that, the release of drug from the prepared gels obeyed the diffusion model (Higuchi’s equation). The results revealed an inverse correlation between the drug release percent and the polymer concentration used. The permeation of drug through skin rat was carried out. The flux of drug is independent on the viscosity of the formulae. The results also showed a significant anti-inflammatory activity on rat paw edema.

This study was designed to evaluate suitability of chitosan polymer as a vehicle for topical delivery system. Quercetin (QUT) is a natural flavonoid, was incorporated into the gel vehicles in a concentration of 0.5% w/v. Gels were prepared with three different concentrations and different molecular weights of chitosan. Viscosity, drug release from prepared gels, permeation of drug through skin rat and anti-inflammatory activity of the drug using carrageenan induced rat paw edema method were studied. In-vitro release characteristics of the drug from different gels were carried out using dialysis membrane in phosphate buffer, pH 5.5. The release data were treated with various kinetic principles to assess the relevant parameters. The general rank order of QUT release was F1 > F4 > F2 > F3 > F5. The results also showed that, the release of drug from the prepared gels obeyed the diffusion model (Higuchi’s equation). The results revealed an inverse correlation between the drug release percent and the polymer concentration used. The permeation of drug through skin rat was carried out. The flux of drug is independent on the viscosity of the formulae. The results also showed a significant anti-inflammatory activity on rat paw edema.

This study was designed to evaluate suitability of chitosan polymer as a vehicle for topical delivery system. Quercetin (QUT) is a natural flavonoid, was incorporated into the gel vehicles in a concentration of 0.5% w/v. Gels were prepared with three different concentrations and different molecular weights of chitosan. Viscosity, drug release from prepared gels, permeation of drug through skin rat and anti-inflammatory activity of the drug using carrageenan induced rat paw edema method were studied. In-vitro release characteristics of the drug from different gels were carried out using dialysis membrane in phosphate buffer, pH 5.5. The release data were treated with various kinetic principles to assess the relevant parameters. The general rank order of QUT release was F1 > F4 > F2 > F3 > F5. The results also showed that, the release of drug from the prepared gels obeyed the diffusion model (Higuchi’s equation). The results revealed an inverse correlation between the drug release percent and the polymer concentration used. The permeation of drug through skin rat was carried out. The flux of drug is independent on the viscosity of the formulae. The results also showed a significant anti-inflammatory activity on rat paw edema.

Background: Sumatriptan succinate (SUT) is a potent drug used for relieving or ending migraine and cluster headaches. SUT bioavailability is low (15%) when it is taken orally owing to its gastric breakdown and bloodstream before reaching the target arteries. Aim: The aim of the study was to enhance SUT bioavailability through developing an intranasal transferosomal mucoadhesive gel. Methods: SUT-loaded nanotransferosomes were prepared by thin film hydration method and characterized for various parameters such as vesicle diameter, percent entrapment efficiency (%EE), in vitro release and ex vivo permeation studies. The in-situ gels were prepared using various ratios of poloxamer 407, poloxamer 188, and carrageenan and characterized for gelation temperature, mucoadhesive strength, and rheological properties. Results: The prepared transferosomes exhibited percent entrapment efficiencies (%EE) of 40.41±3.02 to 77.47±2.85%, mean diameters of 97.25 to 245.01 nm, sustained drug release over 6 hours, and acceptable ex vivo permeation findings. The optimum formulae were incorporated into poloxamer 407 and poloxamer 188-based thermosensitive in-situ gel using carrageenan as a mucoadhesive polymer. Pharmacokinetic evaluation showed that the prepared in-situ gel of SUT-loaded nano-transferosomes gave enhanced bioavailability, 4.09- fold, as compared to oral drug solution. Conclusion: Based on enhancing the bioavailability and sustaining the drug release, it can be concluded that the in-situ gel of SUT-loaded nano-transferosomes were developed as a promising non-invasive drug delivery system for treating migraine.

Abstract: Epigallocatechin-3-gallate (EGCG) is a pleiotropic compound with anticancer, anti-inflammatory, and antioxidant properties. To enhance EGCG anticancer efficacy, it was loaded onto gold nanoparticles (GNPs). EGCG-GNPs were prepared by a simple green synthesis method and were evaluated using different techniques. Hemocompatibility with human blood and in vivo anticancer efficacy in Ehrlich ascites carcinoma-bearing mice were evaluated. EGCG/gold chloride molar ratio had a marked effect on the formation and properties of EGCG-GNPs where well-dispersed spherical nanoparticles were obtained at a molar ratio not more than 0.8:1. The particle size ranged from ~26 to 610 nm. High drug encapsulation efficiency and loading capacity of ~93 and 32%, respectively were obtained. When stored at 4 °C for three months, EGCG-GNPs maintained over 90% of their drug payload and had small changes in their size and zeta potential. They were non-hemolytic and had no deleterious effects on partial thromboplastin time, prothrombin time, and complement protein C3 concentration. EGCG-GNPs had significantly better in vivo anticancer efficacy compared with pristine EGCG as evidenced by smaller tumor volume and weight and higher mice body weight. These results confirm that EGCG-GNPs could serve as an efficient delivery system for EGCG with a good potential to enhance its anticancer efficacy.

Abstract: Epigallocatechin-3-gallate (EGCG) is a pleiotropic compound with anticancer, anti-inflammatory, and antioxidant properties. To enhance EGCG anticancer efficacy, it was loaded onto gold nanoparticles (GNPs). EGCG-GNPs were prepared by a simple green synthesis method and were evaluated using different techniques. Hemocompatibility with human blood and in vivo anticancer efficacy in Ehrlich ascites carcinoma-bearing mice were evaluated. EGCG/gold chloride molar ratio had a marked effect on the formation and properties of EGCG-GNPs where well-dispersed spherical nanoparticles were obtained at a molar ratio not more than 0.8:1. The particle size ranged from ~26 to 610 nm. High drug encapsulation efficiency and loading capacity of ~93 and 32%, respectively were obtained. When stored at 4 °C for three months, EGCG-GNPs maintained over 90% of their drug payload and had small changes in their size and zeta potential. They were non-hemolytic and had no deleterious effects on partial thromboplastin time, prothrombin time, and complement protein C3 concentration. EGCG-GNPs had significantly better in vivo anticancer efficacy compared with pristine EGCG as evidenced by smaller tumor volume and weight and higher mice body weight. These results confirm that EGCG-GNPs could serve as an efficient delivery system for EGCG with a good potential to enhance its anticancer efficacy.

Abstract: The opposing effect of the blood-brain barrier against the delivery of most drugs warrants the need for an efficient brain targeted drug delivery system for the successful management of neurological disorders. Temazepam-loaded nanostructured lipid carriers (NLCs) have shown possibilities for enhancing bioavailability and brain targeting affinity after oral administration. This study aimed to investigate these properties for insomnia treatment. Temazepam-NLCs were prepared by the solvent injection method and optimized using a 42 full factorial design. The optimum formulation (NLC-1) consisted of; Compritol® 888 ATO (75 mg), oleic acid (25 mg), and Poloxamer® 407 (0.3 g), with an entrapment efficiency of 75.2 ± 0.1%. The average size, zeta potential, and polydispersity index were determined to be 306.6 ± 49.6 nm, -10.2 ± 0.3 mV, and 0.09 ± 0.10, respectively. Moreover, an in vitro release study showed that the optimized temazepam NLC-1 formulation had a sustained release profile. Scintigraphy images showed evident improvement in brain uptake for the oral 99mTc-temazepam NLC-1 formulation versus the 99mTc-temazepam suspension. Pharmacokinetic data revealed a significant increase in the relative bioavailability of 99mTc-temazepam NLC-1 formulation (292.7%), compared to that of oral 99mTc-temazepam suspension. Besides, the NLC formulation exhibited a distinct targeting affinity to rat brain. In conclusion, our results indicate that the developed temazepam NLC formulation can be considered as a potential nanocarrier for brain-mediated drug delivery in the out-patient management of insomnia.