A solid dispersion (SD) approach has been performed to enhance the dissolution rate of insoluble drugs by improving their aqueous solubility. An insoluble drug, nimesulide (Nims), was chosen as a model for non-steroidal anti-inflammatory drugs. It was dispersed in a water-soluble carrier poloxamer 407. Different methods were employed to prepare such dispersion, namely: Solvent method (SM), Melting method (MM) and Kneading method (KM) in different drug: carrier ratios. Nims solid dispersions were characterized for their physicochemical properties using scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and the powder X-ray diffractometry (XRD). In addition to dissolution studies, the results revealed that Nims was converted to its amorphous state. The dissolution rate of the prepared solid dispersion systems was determined in phosphate buffer pH 7.4. The solubility of drug from different systems was also determined in water. This study revealed that, the presence of the hydrophilic carrier allows improving the drug solubility. The dissolution rate was enhanced in the following order KM > MM > SM. The enhancement of dissolution rate may be due to increase in wettability, dispersibillity as well as particle size reduction of the drug.

A solid dispersion (SD) approach has been performed to enhance the dissolution rate of insoluble drugs by improving their aqueous solubility. An insoluble drug, nimesulide (Nims), was chosen as a model for non-steroidal anti-inflammatory drugs. It was dispersed in a water-soluble carrier poloxamer 407. Different methods were employed to prepare such dispersion, namely: Solvent method (SM), Melting method (MM) and Kneading method (KM) in different drug: carrier ratios. Nims solid dispersions were characterized for their physicochemical properties using scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and the powder X-ray diffractometry (XRD). In addition to dissolution studies, the results revealed that Nims was converted to its amorphous state. The dissolution rate of the prepared solid dispersion systems was determined in phosphate buffer pH 7.4. The solubility of drug from different systems was also determined in water. This study revealed that, the presence of the hydrophilic carrier allows improving the drug solubility. The dissolution rate was enhanced in the following order KM > MM > SM. The enhancement of dissolution rate may be due to increase in wettability, dispersibillity as well as particle size reduction of the drug.

Surface modification of liposomal nanocarriers with a novel polymer-lectin conjugate was proposed for enhancing the systemic uptake of encapsulated peptide and protein therapeutics after oral administration. Wheat germ agglutinin (WGA) was covalently attached to carbopol (CP) using the carbodiimide method. The prepared WGA-CP conjugate retained the biological cell binding activity of WGA without any evidence of cytotoxicity to Caco-2 monolayers. Cationic liposomes in the size range of 100 nm were prepared by the lipid film hydration method followed by probe sonication and surface modification with negatively charged WGA-CP. The uptake of WGA-CP liposomes by Caco-2 cells was significantly higher than non-modified or CP liposomes. The uptake was dependent on the surface concentration of WGA, temperature, and incubation period, and was significantly inhibited in the presence of chlorpromazine and 10-fold excess of free WGA. These results suggest the involvement of active transport mechanism for the cellular uptake of the modified liposomes, mediated mainly by binding of WGA to its specific cell membrane receptors. Dual channel confocal microscopy confirmed the simultaneous association and internalization of the polymer conjugate and the liposomal carrier by Caco-2 cells and intestinal membrane of rats. In addition, the pharmacological efficacy of calcitonin, a model peptide drug, was enhanced by more than 20 and 3 folds following peroral administration of calcitonin-loaded WGA-CP liposomes as compared to non-modified and CP liposomes, respectively.

Chitosan nanoparticles (CS NPs) have been commonly regarded as potential carriers for the mucosal delivery of therapeutic peptides because of their biocompatibility, bioadhesion and permeation enhancing properties. However, they have limited colloidal stability and readily dissociate and dissolve in the acidic gastric conditions. In the current study, CS NPs were formulated by ionic cross-linking with hydroxypropyl methylcellulose phthalate (HPMCP) as a pH-sensitive polymer and evaluated for the oral delivery of insulin. In vitro results revealed a superior acid stability of CS/HPMCP NPs with a significant control over insulin release and degradation in simulated acidic conditions with or without pepsin. Furthermore, fluorescently-labeled CS/HPMCP NPs showed a 2- to 4-fold improvement in the intestinal mucoadhesion and penetration compared to CS/TPP NPs as evidenced by quantitative fluorescence analysis and confocal microscopy. After s.c. injection to rats, no significant difference in the hypoglycemic effect of insulin solution or insulin-loaded CS/HPMCP NPs was observed, confirming the physico-chemical stability and biological activity of the entrapped peptide. Following peroral administration, CS/HPMCP NPs increased the hypoglycemic effect of insulin by more than 9.8 and 2.8 folds as compared to oral insulin solution and insulin-loaded CS/tripolyphosphate (TPP) NPs, respectively.

A simple, reproducible and efficient dual separation mode high performance liquid chromatographic (HPLC) method was developed for simultaneous determination of antihypertensive drug combinations including; hydrochlorothiazide (HCTZ), valsartan (VAL), amiloride (AML) and captopril (CAP). The newly developed PlatinumTM column, which provides a dual-mode separation with its polar and non-polar sites, was used for rapid separation of these co-administered drugs. Good resolution was obtained when PlatinumTM column was used compared with C18 column. Additionally, simple isocraticmodewith mobile phase containing methanol and 0.02 mole L-1 phosphate buffer adjusted to pH 3.0 (45:55, v/v) was used for separation. The flow rate was 0.5mLmin-1 and effluent was monitored at 270 nm. All the investigated drugs were completely separated within less than 6 min. The linearity range obtained for the developed HPLC method was 0.5–100 μgmL-1 with detection limits of 0.13–1.2 μgmL-1 for all the studied drugs. The method was validated in accordance with the requirements of ICH guidelines and shown to be suitable for -2- intended applications. The method was successfully used for determination of the studied drugs in pure form and pharmaceutical dosage forms without prior need for separation. The method is valuable for quality control laboratories for simultaneous determination of these co-administered antihypertensive drugs in binary, ternary and quaternary mixtures.

A simple, reproducible and efficient dual separation mode high performance liquid chromatographic (HPLC) method was developed for simultaneous determination of antihypertensive drug combinations including; hydrochlorothiazide (HCTZ), valsartan (VAL), amiloride (AML) and captopril (CAP). The newly developed PlatinumTM column, which provides a dual-mode separation with its polar and non-polar sites, was used for rapid separation of these co-administered drugs. Good resolution was obtained when PlatinumTM column was used compared with C18 column. Additionally, simple isocraticmodewith mobile phase containing methanol and 0.02 mole L-1 phosphate buffer adjusted to pH 3.0 (45:55, v/v) was used for separation. The flow rate was 0.5mLmin-1 and effluent was monitored at 270 nm. All the investigated drugs were completely separated within less than 6 min. The linearity range obtained for the developed HPLC method was 0.5–100 μgmL-1 with detection limits of 0.13–1.2 μgmL-1 for all the studied drugs. The method was validated in accordance with the requirements of ICH guidelines and shown to be suitable for -2- intended applications. The method was successfully used for determination of the studied drugs in pure form and pharmaceutical dosage forms without prior need for separation. The method is valuable for quality control laboratories for simultaneous determination of these co-administered antihypertensive drugs in binary, ternary and quaternary mixtures.

A simple, reproducible and efficient dual separation mode high performance liquid chromatographic (HPLC) method was developed for simultaneous determination of antihypertensive drug combinations including; hydrochlorothiazide (HCTZ), valsartan (VAL), amiloride (AML) and captopril (CAP). The newly developed PlatinumTM column, which provides a dual-mode separation with its polar and non-polar sites, was used for rapid separation of these co-administered drugs. Good resolution was obtained when PlatinumTM column was used compared with C18 column. Additionally, simple isocraticmodewith mobile phase containing methanol and 0.02 mole L-1 phosphate buffer adjusted to pH 3.0 (45:55, v/v) was used for separation. The flow rate was 0.5mLmin-1 and effluent was monitored at 270 nm. All the investigated drugs were completely separated within less than 6 min. The linearity range obtained for the developed HPLC method was 0.5–100 μgmL-1 with detection limits of 0.13–1.2 μgmL-1 for all the studied drugs. The method was validated in accordance with the requirements of ICH guidelines and shown to be suitable for -2- intended applications. The method was successfully used for determination of the studied drugs in pure form and pharmaceutical dosage forms without prior need for separation. The method is valuable for quality control laboratories for simultaneous determination of these co-administered antihypertensive drugs in binary, ternary and quaternary mixtures.

Recently, drug nanosuspensions have shown a potential for ophthalmic delivery. In this study, a hydrocortisone (HC) nanosuspension (NS) was developed using microfluidic nanoprecipitation as a recent, simple and cost-effective bottom-up technique of drug nanonization. For comparison, a second HC NS was prepared by top-down wet milling procedures. The produced nanosuspensions were characterized for particle size, shape and zeta potential. HC nanosuspensions of approximately 300 nm particle size were produced by adjusting experimental conditions of the two processing techniques. Results of X-ray diffraction and differential scanning calorimetry revealed that HC maintained the crystalline structure upon milling, while predominant amorphous particles were generated after precipitation. Ocular bioavailability of HC nanosuspensions was assessed in albino rabbits using HC solution as a control. A sustained drug action was maintained up to 9 h for the nanosuspensions compared to 5 h for the drug solution. The precipitated and milled NS achieved comparable AUC0–9h values of 28.06 ± 4.08 and 30.95 ± 2.2, respectively, that were significantly (P 0.05) higher than that of HC solution (15.86 ± 2.7). After 2 months storage at room temperature, the milled HC NS showed good stability with no discernable changes in particle size, whereas the particle size of the precipitated HC NS increased to 440 nm.

The objective of this work was to evaluate the efficacy and suitability of different organogel formulations as transdermal delivery systems of meloxicam (MX) compared to hydrogel formulations. Hydrogels and hydroalcoholic gels were prepared using either carbopol 940 or pluronic F-127 as gelling agents. The organogels used glyceryl monostrearate (GMS), a glyceryl fatty acid ester as organogelator in view of the good skin tolerability of this group of organogelators. The liquid phase was oleic acid, Mygliol 812 or Labrasol. In vitro drug release through cellophane membrane was studied. The effect of some formulation variables (organogelator concentration, type of liquid phase, drug concentration and method of drug incorporation) on the release patterns of meloxicam (MX) from different organogels was investigated. In vitro skin permeation through excised rat skin in phosphate buffer (pH 7.4) was carried out. The in vivo skin penetration was evaluated by measuring the anti-inflammatory effect in rats by the paw edema test. The highest drug release was obtained from Mygliol 812 organogel, Labrasol organogel and hydroalcoholic pluronic gel. The results revealed an inverse correlation between the drug release rate and organogelator concentration and direct correlation between the drug release rate and the initial drug concentration. The release rate of the drug was dependent on the nature of the gel’s liquid component (which influences drug solubility), but not on the method of drug incorporation. Permeation across rat skin showed that Mygliol 812 and Labrasol organogels were superior to hydrogels and hydroalcoholic gels. The anti-inflammatory activity of the drug in different formulations was studied using carragenan-induced rat paw edema method. The results showed an excellent anti-inflammatory activity for the tested formulations, but the anti-inflammatory activity of organogels was significantly higher than that of hydroalcoholic gel. Histopathological examination of rat skin treated with the selected formulations showed normal skin histology. These findings suggest that these organogels could be effective vehicles for transdermal delivery of meloxicam.

Ketorolac tromethamine (KT) is a non-steroidal anti-inflammatory drug having a half half-life around 6 h. This study aims to formulate sustained release forms of KT by preparing solid dispersion in the matrices of Eudragit polymers (Eud) using coevaporation technique. Tow Eud polymers, namely Eud RS100 and Eud RL100, were used in preparing KT-coprecipitates at different drug:polymer ratios. The prepared KT-Eud coprecipitates were characterized for their yield, drug content and drug in vitro release patterns as well. In addition, physicochemical characterization was carried out on some KT-Eud coprecipitates by differential scanning calorimety (DSC) and infrared spectroscopy (IR) so as to study the possibility of solid-state KT-Eud interaction. Also, KT interaction with the tested Eud polymers was carried out in solution in phosphate buffer saline (PBS, pH 7.4) along twenty days. Moreover, the analgesic activity of KT-Eud RS 100 (1: 5) coprecipitate was assessed by tail-flick method and compared to that of untreated KT. The in vitro release results indicated that the dispersions made of pure Eud RS exhibited a slower when compared to those prepared using RS/RL blends. DSC scans of KT-Eud RS 100 (1:5) systems indicated that a complete suppression of the drug fusion peaks suggesting a homogeneous dissolution of the drug in the polymer matrix. Eud RL 100 had a greater adsorptive capacity than Eud RS 100 due to the greater number of quaternary ammonium functions on RL surfaces. The maximum analgesic activity of KT-Eud RS100 (1:5) coprecipitate was between 5 and 6 h extended to 10 h while the maximum analgesic activity of untreated Ketorolac was between 2 and 2.5 h.