OPTIMIZATION AND IN VITRO EVALUATION OF THE RELEASE OF CLASS II DRUG FROM ITS NANOCUBOSOMAL DISPERSION

Objective: This work involves investigation and evaluation of the factors that affect the preparation and the release of the model class II drug (erythromycin) to optimize the efficiency of its prepared nanocubosomal dispersion to give very fast initial burst effect within the first hour that can continue for further two hours. Methods: The work involved preparation of ten formulas of cubosomal dispersion by emulsifying different concentrations of glyceryl monooleate (GMO) (lipid content)/surfactant mixtures which were nano-sized and characterized morphologically by Transmission electronic microscopic (TEM), zeta potential, particle size, polydispersity index (pdI), pH, entrapment efficiency, conductivity test, dilution test and in vitro drug release. Results: The selected nanocubosomal formula (F1) showed pH (7.41), particle size (315.05 nm), pdI (0.194), zeta potential (-30.852), entrapment efficiency (91%) and gave a 70% drug release within the first hour of the in vitro test and continued until it gave 96.3% drug release with further 2 h. Conclusion: this work succeeded in preparing optimized cubosomal dispersion for erythromycin using different GMO/poloxamer 407 percent. The optimum formula gave an immediate release of the model drug (erythromycin) and it was ready to be incorporated in any suitable dosage form to give fast onset of action

ABSOLUTE AND RELATIVE BIOAVAILABILITY STUDY FOR THE NEWLY DEVELOPED NASAL NANOEMULSION IN SITU GEL OF ONDANSETRON HCl IN COMPARISON TO CONVENTIONALLY PREPARED IN SITU GEL AND INTRAVENOUS DOSAGES FORMS

Objective: The aim of the work was to study the absolute and relative bioavailability (using rabbits) of ondansetron HCl (ONH)from our newly prepared intranasal mucoadhesive nanoemulsion in situ gel (NIG) in comparison to intranasal mucoadhesive in situ gel (IG) prepared by the conventional method and intravenous injection.Methods: Six male rabbits weighing 2.5-3 kg were used in this study, where the dose of ondansetron HCl (ONH) was calculated based on the body surface area (BSA) which is equivalent to 140μl (containing 10 mg/ml) of NIG and IG and 700μl of intravenous Zofran® injection (containing 2 mg/ml) were given to the rabbits, separated with one week washout period. Serial blood samples were withdrawn and analyzed for simultaneous determination of the drug using HPLC (Knaure; 150 ×4.6 mm; 5 μm particle size; 25 cm length) supported by guard column C18-4 mm diameter.Results: The pharmacokinetics parameters for NIG; Cmax, Tmax, AUC0-t, AUC0-∞were found to be greater than conventional in situ gel (IG). In vivo pharmacokinetic studies in rabbits showed a significant increase in Cmax and AUC 0-α(P<0.001) with shorter Tmaxusing NIG compared to IG containing the same NIG excipients, while the absolute bioavailability for NIG and IG (was 80.541 and 51.068 respectively).Conclusion: The present studies ratify the bioavailability enhancement potential of NE used to prepare NIG for the drug and significantly high absolute bioavailability to be used as a successful alternative route to the IV injection and improve patient compliance

A newly modified HPLC method for estimation of dutasteride in prepared niosomes

A modify, fast, accurate and precise HPLC conditions were developed and validated for the determination of dutasteride (DT) in niosomes derived from proniosomal gel. The work has shown enough isolation for DT from other contents of the niosomes. The isolation of DT was achieved on C18 column (3μm, 125 × 4.6 mm). The mobile phase was a mixture of acetonitrile: water in a ratio of (50:50) and the flow rate was 1.5 mL per minute. The wave length used to detect dutasteride was 210 nm and the ejection volume was 100 μL. The calibration curve of concentrations range from 50 to 0.3 μg/mL obeys Beer-Lambert's law (R² = 1) for DT. The limits of detection were 0.3 µg/mL for DT with high accuracy and precision which approved that no interaction between the drug and other niosomal content unlike the ordinary UV-spectroscopy and the reported HPLC procedure for DT. 

Factors affecting preparation and evaluation of Kitorolac tromethamine microsponges for ocular use

Ketorolac Tromethamine (KT) is prepared for the first time by double emulsion procedure. The current research involves preparation and evaluation of microsponges for ocular applications. This work included preparation of sixteen formulas of KT-microsponges by double emulsion (w/o/w) method using poly lactic-co-glycolic acid (PLGA) as a polymer and poly vinyl alcohol (PVA) as a stabilizer, with different mixer types for different time and power. The prepared microsponges were characterized by Scanning Electron Microscopy (SEM) to investigate the morphology and particle size, the entrapment efficacy and percentage yield were calculated as well as in vitro drug release. Best formula (F14) of KT-microsponges had EE (74%), % yield (83%) with initial drug release (approximately 21% within the first fifteen days) which continued to reach (approximately 86% within 90 days) by using 30% of  PLGA  concentration with 0.05% of PVA and 200 ml of the external aqueous phase using a probe sonicator for 4 minutes at 200 Watt power. This formulation technique will be the interest of pharmaceutical company

LOADING OF CLARITHROMYCIN AND PACLITAXEL ON SYNTHESIZED CdS/NiO NANOPARTICLES AS PROMISING NANOCARRIERS

Objective: In this study cadmium sulfide (CdS) and nickel oxide (NiO) nanoparticles were synthesized and applied as novel nanocarriers for antibacterial drug clarithromycin (CLA) and anticancer drug paclitaxel (PTX) to improve their physical properties and biological activities.Methods: Cadmium sulfide (CdS) and nickel oxide (NiO) nanoparticles were synthesized by chemical co-precipitation and thermochemical processing techniques respectively and loaded with clarithromycin (CLA) and paclitaxel (PTX) by simple new one-step reaction. Analytical measures including FTIR, PXRD, SEM, AFM, TGA, DSC and zeta potential where used for characterization. The in vitro release, antibacterial as well as anticancer activities were evaluated.Results: Analytical measures revealed that the loading involved physical complex formation rather than chemical modification with the high percent surface loading of the drugs on the nanoparticles. Solubility/dissolution study revealed higher significant* improvement in the solubility of CLA from NiO nanoparticles than that from CdS nanoparticles while the antibacterial activity of CLA was non-significantly improved. For PTX loaded on CdS and NiO nanoparticles showed non-significant change in its solubility, but remarkable significant* increase in its antitumor activity on MCF-7 cell line accompanied with significant* reduction in its cytotoxicity on normal mammary cell line (MCF-10A) indicating the selectivity and targeting of PTX-CdS/NiO nanocarriers with reduced side effects of the drug and the used metal nanocarriers.Conclusion: This work provided most selective and safe delivery system for PTX and best method for enhancement of CLA solubility.Keywords: Clarithromycin (CLA), Paclitaxel (PTX), Cadmium sulfide (CdS) nanoparticles, Nickel oxide (NiO) nanoparticlesÂ

Preparation and in Vitro Evaluation of Soya Lecithin Based Nano Transfersomal Dispersion for Loxoprofen Sodium

This work involves investigation and evaluation of the factors that affect the preparation and release of the model class I drug (loxoprofen sodium) to optimize the efficiency of its prepared nano transfersomal dispersion to give rapid onset of action (burst effect) within the   first 2 hours that can continue for further four hours. The work involved preparation of twenty formulas of transfersomal dispersion by thin film method which were nano-sized by probe sonication and characterized morphologically by Transmission electronic microscopic (TEM), zeta potential, particle size, polydispersity index (pdI), pH, physical appearance, entrapment efficiency, viscosity, transmittance and in vitro drug release. The selected nano transfersomal formula (SF16) showed pH (7.2), particle size (393 nm), pdI (0.259), zeta potential (-25), entrapment efficiency (91%) and gave a 73% drug release within the first 2 hours of the in vitro test and continued until it gave 86.35% drug release after 4 h. This work succeeded in preparing optimized tansfersomal dispersion for loxoprofen sodium using different soya lecithin / edge activator percent and different types of edge activator. The optimum formula gave an immediate release of the model drug (loxoprofen sodium) and it was ready to be incorporated in any suitable dosage form to give continuous drug release

Preparation and evaluation of oral capsules containing apigenin nanocrystals prepared by ultrasonication

This work aims to enhance dissolution rate, increase absorption and bioavailability of Apigenin by formulating it as nanocrystal suspension employing ultrasonic technology. Two different diluents; (5%, 10%) microcrystalline cellulose (MCC) and (2%, 3%) anhydrous lactose were used to prepare hard gelatin capsules for two optimum types for apigenin nanocrystals prepared in our laboratory utilizing ultrasonication technique using 1% tween 80 (F6) and 2% poloxamer 188 (F20). The results showed that the marketed capsules (containing MCC) had about half the dissolution rate than all the prepared nanocrystals capsules formulas, and the nanocrystals prepared with poloxamer gave 90% release within 20 minutes and 100% release with 2 hours with excellent flow properties with no effect of the added diluents while the addition of diluents improved significantly the release of nanocrystals capsules (F6) with 1% tween 80 with good flow properties. The results suggested that utilizing apigenin nanocrystals prepared by ultrasonication technique may improve drug absorption and bioavailability with a reduced required dose

Effect of different mucoadhesive polymers on release of ondansetron HCl from intranasal mucoadhesive in situ gel

The aim of this work was to promote an intranasal mucoadhesive drug allocation system to simplify the systemic delivery of ondansetron HCL (OND-HCl) for the immediate and sustain prevention of repeated nausea and vomiting caused by the initial and repeated courses of anticancer therapy. An in situ gel dosage form was used to raise the permanence time and hence the absorption of OND-HCl from nasal mucosa. Temperature stimulated in situ gel formulations were intended by cold method using polymers like kolliphor 407, chitosan and HPMC E15. A mixture of polysorbate 20 and ethanol (1: 2 ratio) was used as solvent to dissolve the drug. The pH of in situ gel solution was measured to pH range (4.5-6.5). The six in situ gel formulas were characterized for gelation temperature, pH, viscosity, drug content, mucoadhesion and dissolution release .The temperatures of conversion of all the formulas solution to gel were within the range of 30–43ºC. The drug content of all six in situ gel formulas showed drug content uniformity (99.15–99.76%). Dissolution release of the drug from in situ gel formulas showed immediate and sustained release features with Higuchi model and zero order model mechanisms

Preparation and Evaluation of Microencapsulated Dexamethasone Sodium Phosphate Using Double Emulsion Method

The need for producing sustained release dosage form was increased (especially for chronic diseases) to decrease side effect, increase efficacy of treatment, so it is now possible to administer the drugs once a week to once a year.     Dexamethasone sodium Phosphate (DSP) is a potent corticosteroid used for the treatment of many conditions like osteoarthritis (OA) and post joint replacement surgery. Microencapsulated dexamethasone sodium phosphate (DSP) having continuous prolonged release was prepared. To achieve that, DSP microcapsules were prepared using w/o/w double emulsion method where PLGA was used as a polymer, PVA and glycerol as plasticizer and Cetyl trimethyl ammonium bromide (CTAB) as emulsifying agent. Nine formulas of (PLGA coated (DSP) (microcapsules) were prepared to study the effect of different variables on the % yield and entrapment efficiency (EE) including the effect of internal aqueous phase volume, presence of NaCl (as osmotic pressure enhancer), PLGA concentration, plasticizer concentration and sonication time. The best formula was found to be formula (F1) containing 16 mg DSP coated with PLGA and found to give 85% EE and 94.19% yield

COMPARATIVE BIOAVAILABILITY (BIOEQUIVALENCE) STUDY FOR FIXED DOSE COMBINATION TABLET CONTAINING AMLODIPINE, VALSARTAN, AND HYDROCHLOROTHIAZIDE USING A NEWLY DEVELOPED HPLC-MS/MS METHOD

Objective: The aim of the study was to evaluate the bioequivalence between a newly developed generic tablet containing fixed-dose combination of amlodipine besylate, valsartan and hydrochlorothiazide (10/160/25 mg), and the reference brand product Exforge HCT® tablet; using a newly developed HPLC-MS/MS method for simultaneous determination of these drugs in human plasma.Methods: The brand (reference) and the test (generic) products were administered to thirty-nine healthy subjects. A fasting, laboratory blind, single-dose, two-treatment, two-period, two-sequence, randomized crossover design was conducted with 14 d washout period between dosing. Serial blood samples were withdrawn from each subject immediately before dosing (zero time), and then at 0.33, 0.66, 1.0, 1.33, 1.66, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10, 11, 12, 14, 16, 24, 48 and eventually at 72 h post dosing. Plasma samples were analyzed for simultaneous determination of amlodipine, valsartan and hydrochlorothiazide by a newly developed HPLC coupled with MS/MS detector. The linearity of the method was established for plasma concentration ranges of 0.2-12 ng/ml, 50-8000 ng/ml, and 2-250 ng/ml for amlodipine, valsartan, and hydrochlorothiazide, respectively.Results: Plasma concentration-time data of each individual were analyzed by non-compartmental method to measure the pharmacokinetics parameters; Cmax, Tmax, AUC0-t, AUC0-¥, lZ, T1/2. For amlodipine truncated AUC72hr was calculated. The 90% confidence interval for the pharmacokinetic parameters used for bioequivalence evaluation (Cmax and AUC) for amlodipine, valsartan, and hydrochlorothiazide were well within FDA acceptable ranges of 80-125%.Conclusion: It is concluded that the newly devolved generic product is bioequivalent with the brand product Exforge HCT® tablet. Thus, both products are clinically interchangeable.Keywords: Amlodipine, Valsartan, Hydrochlorothiazide, Pharmacokinetics, Bioequivalence, HPLC-MS/M