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.

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.

This study employs artificial neural networks (ANNs) to create a model to identify relationships between variables affecting drug nanoprecipitation using microfluidic reactors. The input variables examined were saturation levels of prednisolone, solvent and antisolvent flow rates, microreactor inlet angles and internal diameters, while particle size was the single output. ANNs software was used to analyse a set of data obtained by random selection of the variables. The developed model was then assessed using a separate set of validation data and provided good agreement with the observed results. The antisolvent flow rate was found to have the dominant role on determining final particle size.

In this work, the possibility of bottom-up creation of a relatively stable aqueous hydrocortisone nanosuspension using microfluidic reactors was examined. The first part of the work involved a study of the parameters of the microfluidic precipitation process that affect the size of generated drug particles. These parameters included flow rates of drug solution and antisolvent, microfluidic channel diameters, microreactors inlet angles and drug concentrations. The experimental results revealed that hydrocortisone nano-sized dispersions in the range of 80–450 nm were obtained and the mean particle size could be changed by modifying the experimental parameters and design of microreactors. The second part of the work studied the possibility of preparing a hydrocortisone nanosuspension using microfluidic reactors. The nano-sized particles generated from a microreactor were rapidly introduced into an aqueous solution of stabilizers stirred at high speed with a propeller mixer. A tangential flow filtration system was then used to concentrate the prepared nanosuspension. The nanosuspension produced was then characterized using photon correlation spectroscopy (PCS), Zeta potential measurement, transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and X-ray analysis. Results showed that a narrow sized nanosuspension composed of amorphous spherical particles with a mean particle size of 500 ± 64 nm, a polydispersity index of 0.21 ± 0.026 and a zeta potential of −18 ± 2.84 mV was obtained. Physical stability studies showed that the hydrocortisone nanosuspension remained homogeneous with slight increase in mean particle size and polydispersity index over a 3-month period.

Simple, sensitive and precise spectrophotometric and chromatographic methods were developed for simultaneous determination of Sodium cromoglicate (SCG) and Xylometazoline hydrochloride (XYLO) in their pure form and nasal solution. By applying the spectrophotometric methods, (SCG) was determined by direct spectrophotometry through measuring its zero-order (D0) absorption spectra at 325 nm; while (XYLO)was determined using two methods. The first method utilized the first derivative spectra D1 of (XYLO) after prior separation of SCG from medium using 0.1 N HCl. The second method depends on derivative compensation ratio technique depending on the mean ratio of D1 peak amplitudes of SCG (D231.4 / D309.4). The chromatographic method utilized a Zorbax SB-C18 column and a mobile phase of acetonitrile: 10 mM phosphate buffer (pH 4): triethylamine, in ratio (80: 19.9: 0.1 v/v/v), delivered at flow rate of 1.2 mL/min and the detections were done at 220 nm. The proposed methods were validated in compliance with the ICH guidelines and were successfully applied for the analysis of (SCG) and (XYLO) in the laboratory prepared mixtures and combined pharmaceutical dosage form.

Oral mucositis is one of the main complications of non-surgical cancer treatments. The present work focuses on the treatment or reduction of oral mucositis by using combined mechanism by formation of physical barrier by forming a film to cover the oral ulcer and use of therapeutic agents, such as diclofenac sodium and ofloxacin separately or in combination. The selected polymers for film forming gel formulations are Hydroxypropylcellulose (HPC), hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose (Na CMC) and carbopol 940 (CP). The residence time in simulated buccal saliva was between 5.5 to 6 hours for all formulations. The in-vitro release data of the investigated drugs from the prepared formulations followed zero-order and diffusion mechanism. The permeability studies data revealed that diclofenac sodium showed higher permeability from Na CMC/CP (2:0.3%) than from HPMC 4%, while in case of ofloxacin higher permeability was shown from Na CMC/CP (2:0.3%) than from HPMC/HPC (2:3%). The permeation parameters for diclofenac sodium and ofloxacin in their combination do not depend on either viscosity or pH, they depend on the type of polymers used.