The present work focuses on treatment of glaucoma by formulating ocular inserts of different polymeric combination and Timolol maleate to enhance therapeutic effect through prolonging contact time with corneal surface, accurate, and sustain the release of the drug over a long period. The selected polymers for formulation of ocular inserts are Methyl Cellulose (MC), Hydroxypropyl cellulose (HPC), Eudragit RL100 (ERL100), Eudragit RS100 (ERS100), Ethylcellulose (EC), Polyvinylpyrrolidone (PVP). Films were plasticized using different plasticizers. The prepared ocular inserts were evaluated for their mechanical properties and physico-chemical properties. Accelerated stability studies were conducted to investigate the change in appearance, pH, and drug content after storage in drastic conditions. In-vitro drug release and kinetics of drug release from different formulations were studied. In-vitro permeation study was conducted on selected formulations showed better results in previous studies. In-vivo release study was conducted on rabbits after sterilization of ocular inserts by gamma radiation. Intraocular pressure was measured at different time intervals using Schotz tonometer. The in-vitro release data of Timolol maleate from the prepared formulations followed diffusion mechanism. The permeability studies data revealed that the permeability coefficient was found to be dependent on polymer type, the higher the solubility of the polymer the higher permeability coefficient. The reduction in IOP for F3 (HPC/ERL100 5:1), F7 (MC/ERL100 1:1), and F8 (MC/ERL100 1:3) was prolonged for 120 hours (5 days), and 96 hours (4 days) for F12 (HPC/EC 15:1).

The present work describes the synthesis and evaluation of some new acetohydrazones, 1,3,4-oxadiazoles and 1,2,4-triazoles of 1,2,4-triazolo[1,5-a]benzimidazole as anti-inflammatory-analgesic agents. Structure elucidation of these compounds was confirmed by IR, 1H NMR, and mass spectrometry along with elemental microanalyses. Most compounds exhibited significant anti-inflammatory activity in comparison to indomethacin. Further, some compounds were tested for their analgesic effects where two compounds showed results comparable to indomethacin at 4 h interval. The most active anti-inflammatory and analgesic compounds (4c and 11a) were examined on gastric mucosa and didn’t show any gastric ulcerogenic effect compared with the reference indomethacin. Moreover, LD50 of compounds (4c and 11a) were determined in mice; they were found non toxic up to 240 and 300 mg/kg (i.p.). Also, docking simulation of some compounds into COX active sites was studied.

The present work describes the synthesis and evaluation of some new acetohydrazones, 1,3,4-oxadiazoles and 1,2,4-triazoles of 1,2,4-triazolo[1,5-a]benzimidazole as anti-inflammatory-analgesic agents. Structure elucidation of these compounds was confirmed by IR, 1H NMR, and mass spectrometry along with elemental microanalyses. Most compounds exhibited significant anti-inflammatory activity in comparison to indomethacin. Further, some compounds were tested for their analgesic effects where two compounds showed results comparable to indomethacin at 4 h interval. The most active anti-inflammatory and analgesic compounds (4c and 11a) were examined on gastric mucosa and didn’t show any gastric ulcerogenic effect compared with the reference indomethacin. Moreover, LD50 of compounds (4c and 11a) were determined in mice; they were found non toxic up to 240 and 300 mg/kg (i.p.). Also, docking simulation of some compounds into COX active sites was studied.

The present work describes the synthesis and evaluation of some new acetohydrazones, 1,3,4-oxadiazoles and 1,2,4-triazoles of 1,2,4-triazolo[1,5-a]benzimidazole as anti-inflammatory-analgesic agents. Structure elucidation of these compounds was confirmed by IR, 1H NMR, and mass spectrometry along with elemental microanalyses. Most compounds exhibited significant anti-inflammatory activity in comparison to indomethacin. Further, some compounds were tested for their analgesic effects where two compounds showed results comparable to indomethacin at 4 h interval. The most active anti-inflammatory and analgesic compounds (4c and 11a) were examined on gastric mucosa and didn’t show any gastric ulcerogenic effect compared with the reference indomethacin. Moreover, LD50 of compounds (4c and 11a) were determined in mice; they were found non toxic up to 240 and 300 mg/kg (i.p.). Also, docking simulation of some compounds into COX active sites was studied.

Two novel microwell-based spectrophotometric methods with high throughput have been developed and validated for the determination of ciprofloxacin (CIP), a fluoroquinolone antimicrobial agent. These methods were based on the formation of colored condensation products upon reaction of CIP with each of 1,2-naphthoquinone-4-sulphonic acid sodium salt (NQS) and the oxidized pyrocatechol (OPC). These reactions were carried out in a 96-microwell plate and the absorbance of the colored-product was measured by a microwell plate absorbance reader at 460 and 510 nm for NQS and OPC, respectively. The variables affecting the reactions were carefully investigated and the conditions were optimized. The stoichiometry of the reaction was determined, and the reactions pathways were postulated. The proposed reactions were found to be highly selective for CIP among many fluoroquinolone members. Under the optimum conditions, good linear relationships were obtained between the absorbances and the concentrations of CIP in the ranges of 25–200 and 40–450 μg/mL with limits of detections of 3.66 and 8.79 mg/mL for the methods based on NQS and OPC, respectively. The robustness and ruggedness of the methods were satisfactory. The methods were successfully applied to the bulk drug and pharmaceutical dosage forms; the percentage recoveries were 98.0-101.5 (0.45 ± 1.63%). The results were compared favorably with those obtained by a pre-validated reference method; no significant difference in accuracy and precision as revealed by the accepted values of t– and F–tests, respectively.

Two novel microwell-based spectrophotometric methods with high throughput have been developed and validated for the determination of ciprofloxacin (CIP), a fluoroquinolone antimicrobial agent. These methods were based on the formation of colored condensation products upon reaction of CIP with each of 1,2-naphthoquinone-4-sulphonic acid sodium salt (NQS) and the oxidized pyrocatechol (OPC). These reactions were carried out in a 96-microwell plate and the absorbance of the colored-product was measured by a microwell plate absorbance reader at 460 and 510 nm for NQS and OPC, respectively. The variables affecting the reactions were carefully investigated and the conditions were optimized. The stoichiometry of the reaction was determined, and the reactions pathways were postulated. The proposed reactions were found to be highly selective for CIP among many fluoroquinolone members. Under the optimum conditions, good linear relationships were obtained between the absorbances and the concentrations of CIP in the ranges of 25–200 and 40–450 μg/mL with limits of detections of 3.66 and 8.79 mg/mL for the methods based on NQS and OPC, respectively. The robustness and ruggedness of the methods were satisfactory. The methods were successfully applied to the bulk drug and pharmaceutical dosage forms; the percentage recoveries were 98.0-101.5 (0.45 ± 1.63%). The results were compared favorably with those obtained by a pre-validated reference method; no significant difference in accuracy and precision as revealed by the accepted values of t– and F–tests, respectively.

The present study aims to investigate the possibility of interaction of donepezil (DP) and galantamine (GAL) as acetylcholinestrase inhibitors, on memantine (MT) hydrochloride in rat plasma by HPLC-fluorescence detection. The separation of MT was achieved within 12 min without interference of DP and GAL on the chromatogram. MT levels in rat plasma with a single administration of MT (2.5 mg/kg, i.p.) and those with a co-administration of DP (5.0 mg/kg, i.p.) and GAL (3 mg/kg, i.p.) were monitored. MT concentrations determined in rat plasma ranged from 10.0 to 245.6 ng/mL. Significant difference was observed in the behavior of MT with a co-administration of DP, while no significant difference was observed with a co-administration of GAL.

The aim of this study was to synthesize and evaluate novel biodegradable polyesters namely; poly(ethylene glycol)-Poly(glycerol adipate-co--pentadecalactone), PEG-PGA-co-PDL-PEG, and poly(ethylene glycol methyl ether)-Poly(glycerol adipate-co--pentadecalactone), PGA-co-PDL-PEGme as an alternative sustained release carrier for lung delivery compared with non-PEG containing polymer PGA-co-PDL. The co-polymers were synthesized through lipase catalysis ring opening polymerization reaction and characterized using GPC, FT-IR, 1H-NMR and surface contact angle. Furthermore, microparticles containing a model hydrophilic drug, sodium diclofenac, were prepared via spray drying from a modified single emulsion and characterized for their encapsulation efficiency, geometrical particle size, zeta potential, tapped density, primary aerodynamic diameter, amorphous nature, morphology, in vitro release and the aerosolization performance. Microparticles fabricated from mPEG-co-polymer can be targeted to the lung periphery with an optimum in vitro deposition. Furthermore, a significantly higher in vitro release (p>0.05, ANOVA/Dunnett’s) was observed with the PEG and mPEG-co-polymers compared to PGA-co-PDL. In addition, these co-polymers have a good safety profile upon testing on human bronchial epithelial, 16HBE14o- cell lines.

A simple and selective micellar electrokinetic chromatographic (MEKC) method has been developed for the analysis of five pharmaceutical binary mixtures containing three non-steroidal anti-inflammatory drugs (NSAIDs). The investigated mixtures were Ibuprofen (IP)–Paracetamol (PC), Ibuprofen (IP)–Chlorzoxazone (CZ), Ibuprofen (IP)–Methocarbamol (MC), Ketoprofen (KP)– Chlorzoxazone (CZ) and Diclofenac sodium (DS)–Lidocaine hydrochloride (LC). The separation was run for all mixtures using borate buffer (20 mM, pH 9) containing 15% (v/v) methanol and 100 mM sodium dodecyl sulphate (SDS) at 15 kV and the components were detected at 214 nm. Different factors affecting the electrophoretic mobility of the seven investigated drugs were studied and optimized. The method was validated according to international conference of harmonization (ICH) guidelines and United States pharmacopoeia (USP). The method was applied to the analysis of five pharmaceutical binary mixtures in their dosage forms. The results were compared with other reported high performance liquid chromatographic methods and no significant differences were observed.

We described the health resource utilisation (HRU) and associated direct medical costs of managing epilepsy in children and young people (CYP) using population-level data from the United Kingdom. The study cohort were CYP born between 1988 and 2004 who were newly diagnosed with epilepsy and identified using a nationally representative primary care database from the United Kingdom. Reference unit costs were applied to each element of HRU to calculate annual direct medical costs per child. We assessed whether HRU and costs differed by time from diagnosis, age, sex and socioeconomic deprivation. Of 798 CYP newly diagnosed with epilepsy, 56% were male and the mean age at diagnosis was 5.6 years. The highest burden of HRU was in the first year following diagnosis with a mean annual cost of £930 (95% confidence interval (CI) £839-1022) per child in this first year. This decreased to £461 (95%CI 368-551) in the second year which remained fairly constant each subsequent year (£413 (95% CI 282-540) in the 8th year). The highest contribution to the annual medical costs was from inpatient hospital admissions followed by the costs of AEDs. Mean annual medical costs were significantly higher in children under 6 years of age compared with older children (p 0.01), but were similar across socioeconomic groups (p = 0.62). The direct medical costs of HRU in CYP with epilepsy are higher in the first year after diagnosis compared to subsequent years, reflecting HRU related to the diagnostic process in the first year. Medical costs did not vary substantially by sex or socioeconomic deprivation indicating a similar level of consultation and care across these groups.