Effect of Indion Complexation on the Stability and Bioavailability of some Non-steroidal Anti-inflammatory Drugs

Ion exchange resins are commonly used for masking of drug objectionable taste. Our work aimed to study the effect of this complexation on the drug stability and bioavailability in rabbits. In this work, paracetamol and ibuprofen complexes with indion 204 were prepared; drug stability and bioavailability from the prepared complexes were studied and compared with that of the commonly used commercial tablets Tylenol and Motrin respectively. The clinical protocol and information about drugs were discussed with a group of healthy albino rabbits. The results showed that tmax of both drugs were kept constant at 1.5hrs and 2hrs without any change from the reference standards Tylenol and Motrin respectively. The calculated pharmacokinetic parameters Cpmax, AUC(0-24) and AUC(0-∞) respectively for paracetamol were 0.431µg/ml, 3.535µg.hr/ml and 3.756µg.hr/ml from the prepared complexes in comparison to 0.494µg/ml, 4.083µg.hr/ml, 4.198µg.hr/ml from Tylenol, and 0.743µg/ml, 5.380µg.hr/ml, 5.559µg.hr/ml from the prepared ibuprofen complexes in comparison to 0.803µg/ml, 6.272 µg.hr/ml, 6.432 µg.hr/ml from Motrin. The relative bioavailability of both drugs from the prepared complexes were calculated using Tylenol and Motrin as reference standards and the 90 % confidence intervals of the geometric mean values for the test/reference ratios for Cpmax, AUC (0-24) and AUC (0-∞) were within the bioequivalence acceptance range of 80–125 % according to the European Guideline. Statistical analysis (ANOVA) indicated a significance difference between the calculated pharmacokinetic parameters for both drugs. From these results we can conclude that indion complexation of drugs significantly affects their pharmacokinetics and retards their bioavailability

Ketorolac Tromethamine In-situ Ocular Hydro Gel; Preparation, Characterization, and In-vivo Evaluation

The aim of this work is to formulate Ketorolac tromethamine in a new ocular in situ hydro gel delivery system. Two polymers; Chitosan and Carbopol 940 were used in different concentrations for the preparation of the in situ hydro gels, all formulations exposed to visual examination, pH measurement, in-vitro release, rheological study, stability study, and in-vivo anti-inflammatory effect study on the inflamed eye of rabbits. Results showed that all formulations were clear and showed pH within the acceptable range, Chitosan 0.5%w/v gives the highest release rate, all formulae exhibited pseudoplastic flow with a thixotropic behavior, stability study showed that rate of drug degradation followed first order kinetics and 0.5% Chitosan based formula showed longer shelf life (2.532 year), the percent of unhealed ulcers of the inflamed eye of rabbits was 17.5% for 0.5% Chitosan in situ hydro gel compared to 55% for Acular eye drop (positive control). Statistical analysis of the data revealed significance difference between the tested formula and control solution at p <0.05. So this system that combines the advantages of both solutions and gels, such as accuracy and facility of administration of the former and prolonged residence time of the latter, also enhances the healing rate of Ketorolac tromethamine in ulcerative rabbit's eye compared to ocular eye drops

Formulation and in-vitro evaluation of fast dissolving tablets containing a poorly soluble antipsychotic drug

The aim of the present study was to formulate olanzapine fast dissolving tablets (FDT). Olanzapine is a poorly water soluble drug that undergoes first pass metabolism in liver resulted in low oral bioavailability. The water solubility is enhanced by formation of co-amorphous dispersion by solvent evaporation under vacuum method using a polycarboxylic acid (ascorbic acid) as a coformer in two different molar ratios (1:1 and 1:2). The prepared systems were evaluated using differential scanning calorimeter (DSC), Fourier Transform Infra-Red analysis (FTIR), X-ray powder diffraction (XRPD), Scanning electron microscopy (SEM) and saturated solubility. The co-amorphous dispersion system in a molar ratio 1:2 is higher in solubility than 1:1, so it was selected for incorporation into FDT formulation. Compatability study between olanzapine and different tablet excipients including DSC and FTIR showed that the drug is compatible with the selected tablet excipients. Direct compression method was used in FDT formulations using different types and concentrations of superdisintegrants. FDTs were evaluated for weight variation, hardness, friability, wetting time, drug content uniformity, invitro disintegration time and invitro dissolution study. All the prepared FDTs were complied with the compendia standards. F3 and F8 showed lower disintegration time and higher percent of drug dissolved, so they were selected for stability study. After storage for 3 months at 30ºC at 65% relative humidity, both formulations were physically stable regarding color and integrity and had only minor increases in disintegration time, drug content and friability after three months’ storage. The results indicate that olanzapine FDT tablets may serve as a successful strategy for enhancing the bioavailability of olanzapine

INCLUSION AND CHARACTERIZATION OF KETOPROFEN INTO DIFFERENT MESOPOROUS SILICA NANOPARTICLES USING THREE LOADING METHODS

Objective: The objective of the present study was to encapsulate ketoprofen into MCM-41, SBA-15 and uncalcined SBA-15 (unc SBA-15) using different loading methods. Investigate the effect of using different loading methods, and the effect of pore sizes on the loading capacity of mesoporous silica. Finally, determine if any changes in the mesoporous structure occurred after KP loading. Methods: Ketoprofen (KP) with about 1.5 nm molecular size was selected for encapsulation into three mesoporous silica nanoparticles (MSN). These MSN particles were selected to cover a wide range of pore diameters: MCM-41 (3.4 nm), SBA-15 (6.2 nm) and uncalcined SBA-15 (7.0 nm). Loading of KP was done by three loading methods namely rotavapor, soaking, and immersion method. The loading capacity was examined via solvent extraction. Characterization of the loaded mesoporous silica nanoparticles was done by high resolution transmission electron microscopy (HRTEM), small angle X-ray diffraction (SAXRD), nitrogen adsorption/desorption isotherms, differential scanning calorimetry (DSC), and Fourier transform infrared (FT-IR) spectroscopy. Results: KP was successfully encapsulated into MCM-41, SBA-15 and uncalcined SBA-15 without affecting the mesoporous structure. The loading process was done using three different loading methods. Rotavapor loading method yielded higher loading capacities compared to soaking and immersion method. Another important factor that affected the amount of loaded KP into MSN particles were the Pore sizes of the host particles. MCM-41, which had the smallest pore size, had the least amount of loaded drug. On the other hand, uncalcined SBA-15, which had the largest pore size, had the highest amount of loaded KP. Conclusion: This study is a promising issue for the incorporation of KP into different mesoporous silica nanoparticles

Formulation and Evaluation of Taste-Masked Orally Disintegrating Tablets of Nicergoline based on β-cyclodextrin Inclusion Complexation

Complexation of nicergoline with β-cyclodextrin (β-CD) into an inclusion complex has been used successfully to improve the drug’s solubility, dissolution rate and hence per oral absorption. In addition, masking of the bitter taste was also achieved. The preparation of inclusion complexes was performed using two different techniques, namely; physical mixing and kneading. The apparent stability constant (Kc) of the complex was calculated from the phase solubility analysis. Compatibility of nicergoline and β-CD complex with disintegrants and superdisintegrants were evaluated using powder x-ray diffractometry (PXRD), differential scanning calorimetry (DSC), and fourier transform infrared spectroscopy (FTIR). The morphology of complex particles was studied using scanning electron microscopy. Pharmaceutical characterization confirmed that all additives were compatible with the drug and no signs of physical or chemical interaction were detected. Orodispersible tablets (ODTs) of nicergoline complexed with β-CD and containing 7-9 % camphor had rapid disintegration time (7-12 seconds) and fast drug release profiles (90-100 % in 10 minutes). Therefore, nicergoline ODTs are considered a valuable choice dosage form with improved per oral absorption and taste acceptability

DEVELOPMENT AND IN VITRO EVALUATION OF MUCOADHESIVE BILAYER BUCCAL TABLETS OF CARVEDILOL

Objectives: Carvedilol (CVD) is a nonselective β-adrenergic blocker that suffers from low absolute bioavailability (25-35%) due to first-pass metabolism. CVD-loaded buccal tablets were developed as a promising approach to overcome this limitation.Methods: The bilayers tablets were prepared by the direct compression technique. CVD-containing layer was based on one of four high molecular weight polymers; hydroxy propyl methylcellulose K15M (HPMC), Polyethylene oxide WSR N-750 (PEO), chitosan (CH) and Eudragit® RS-100 (EUD). An occlusive backing of ethylcellulose 20 (Ethocel®) was adopted as a second layer. The tablets were characterized for weight variation, thickness, friability % and drug content. Further studies were conducted to evaluate their swelling indices, surface pH, in vitro adhesion retention periods and in vitro drug release profiles.Results: The prepared tablets followed the compendial requirements for thickness, friability %, drug content and weight variation. The surface pH of all tablets ranged from 6.43 to 7.44 while their adhesion retention periods varied from 3.12 to 4.24 h. The best achieved system (PEO-based matrix; F4) displayed a reasonable adhesion retention period and a promising sustained drug release profile, over at least 8 hours, following non-fickian diffusion kinetics. This could indicate the contribution of swelling and erosion mechanisms for drug release.Conclusions: The current work succeeded in developing and evaluation of promising mucoadhesive CVD matrices suitable for buccal administration. Further pharmacokinetic and clinical studies are suggested to confirm the ability of the best achieved system to avoid the first pass metabolism of CVD and improve patient compliance.Â

Formulation and Evaluation of Taste-Masked Orally Disintegrating Tablets of Nicergoline based on β-cyclodextrin Inclusion Complexation

Complexation of nicergoline with β-cyclodextrin (β-CD) into an inclusion complex has been used successfully to improve the drug’s solubility, dissolution rate and hence per oral absorption. In addition, masking of the bitter taste was also achieved. The preparation of inclusion complexes was performed using two different techniques, namely; physical mixing and kneading. The apparent stability constant (Kc) of the complex was calculated from the phase solubility analysis. Compatibility of nicergoline and β-CD complex with disintegrants and superdisintegrants were evaluated using powder x-ray diffractometry (PXRD), differential scanning calorimetry (DSC), and fourier transform infrared spectroscopy (FTIR). The morphology of complex particles was studied using scanning electron microscopy. Pharmaceutical characterization confirmed that all additives were compatible with the drug and no signs of physical or chemical interaction were detected. Orodispersible tablets (ODTs) of nicergoline complexed with β-CD and containing 7-9 % camphor had rapid disintegration time (7-12 seconds) and fast drug release profiles (90-100 % in 10 minutes). Therefore, nicergoline ODTs are considered a valuable choice dosage form with improved per oral absorption and taste acceptability

Effect of Indion Complexation on the Stability and Bioavailability of some Non-steroidal Anti-inflammatory Drugs

Ion exchange resins are commonly used for masking of drug objectionable taste. Our work aimed to study the effect of this complexation on the drug stability and bioavailability in rabbits. In this work, paracetamol and ibuprofen complexes with indion 204 were prepared; drug stability and bioavailability from the prepared complexes were studied and compared with that of the commonly used commercial tablets Tylenol and Motrin respectively. The clinical protocol and information about drugs were discussed with a group of healthy albino rabbits. The results showed that tmax of both drugs were kept constant at 1.5hrs and 2hrs without any change from the reference standards Tylenol and Motrin respectively. The calculated pharmacokinetic parameters Cpmax, AUC(0-24) and AUC(0-∞) respectively for paracetamol were 0.431µg/ml, 3.535µg.hr/ml and 3.756µg.hr/ml from the prepared complexes in comparison to 0.494µg/ml, 4.083µg.hr/ml, 4.198µg.hr/ml from Tylenol, and 0.743µg/ml, 5.380µg.hr/ml, 5.559µg.hr/ml from the prepared ibuprofen complexes in comparison to 0.803µg/ml, 6.272 µg.hr/ml, 6.432 µg.hr/ml from Motrin. The relative bioavailability of both drugs from the prepared complexes were calculated using Tylenol and Motrin as reference standards and the 90 % confidence intervals of the geometric mean values for the test/reference ratios for Cpmax, AUC (0-24) and AUC (0-∞) were within the bioequivalence acceptance range of 80–125 % according to the European Guideline. Statistical analysis (ANOVA) indicated a significance difference between the calculated pharmacokinetic parameters for both drugs. From these results we can conclude that indion complexation of drugs significantly affects their pharmacokinetics and retards their bioavailability

Ketorolac Tromethamine In-situ Ocular Hydro Gel; Preparation, Characterization, and In-vivo Evaluation

The aim of this work is to formulate Ketorolac tromethamine in a new ocular in situ hydro gel delivery system. Two polymers; Chitosan and Carbopol 940 were used in different concentrations for the preparation of the in situ hydro gels, all formulations exposed to visual examination, pH measurement, in-vitro release, rheological study, stability study, and in-vivo anti-inflammatory effect study on the inflamed eye of rabbits. Results showed that all formulations were clear and showed pH within the acceptable range, Chitosan 0.5%w/v gives the highest release rate, all formulae exhibited pseudoplastic flow with a thixotropic behavior, stability study showed that rate of drug degradation followed first order kinetics and 0.5% Chitosan based formula showed longer shelf life (2.532 year), the percent of unhealed ulcers of the inflamed eye of rabbits was 17.5% for 0.5% Chitosan in situ hydro gel compared to 55% for Acular eye drop (positive control). Statistical analysis of the data revealed significance difference between the tested formula and control solution at p <0.05. So this system that combines the advantages of both solutions and gels, such as accuracy and facility of administration of the former and prolonged residence time of the latter, also enhances the healing rate of Ketorolac tromethamine in ulcerative rabbit's eye compared to ocular eye drops

Towards Sustainable Management of Coastal and Offshore Islands in Arabian Gulf Typology: Sensitivity Analysis, Ecological Risk Assessment of Halul and Al-Alyia Islands

The great majority of marine ecosystems in Qatar are in fast decline and nearing collapse, where most ecosystem has lost the biological and economic functionality. Aiming to support the decision makers in the management and restoration strategies for recovering the biological and economic functionality of the ecosystems/natural resources of Qatar, we conducted 1) a typology mapping of the main components of the ecosystem of two islands, 2) a sensitivity and vulnerability assessment according to the known guidelines and standards. Highlighting the potential ecological risk and required recommendations for sustainable management plans, within the frame of Qatar National Vision 2030 (QNV 2030). The Islands present different anthropogenic pressure. As expected, Al Alyia the coastal Island is under real risk, with critical areas of sensibility but still presenting a potential for recovering its economy and ecological functionality, highlighting the collapsed stage of the very sensitive coral reefs, the vulnerability of oyster beds and seagrass and the functionality of the mangrove (expanding) and Sabha with massive birds nesting. The offshore Island Halul presented in the typology mapping the coral reefs as the main ecosystem but with the presence of seagrass, algae bed, sandy beach, and Sabha. The coral reef still presents a certain functionality, with corals covering several hard substrates, however with high sensitivity and high vulnerability, especially the coral in the shallow areas with scattered colonies, and the vulnerable nesting of marine turtles on beaches. As the management, we recommend increasing the restoration effort of targeted ecosystems, mainly involving coral reefs for increasing the marine biodiversity in general and restoring the oyster beds for recovering the filtration service. Strategies must be made for recovering the ecosystems' functionality and restore the productivity of the Qatari fishing stock. We recommend applying this mapping method and sensitivity classification for all marine areas around Qatar for supporting the management plans