Yasir Almajidi

Meclizine HCl (MCZ) is a first-generation antihistamine of the piperazine class drug that possesses anticholinergic and antispasmodic effect. It has low and variable bioavailability attributed to its low solubility in water. There are many methods used to increase the rate of dissolution of the drug and in this study, nanosuspension preparation enhanced the dissolution of the drug. Meclizine HCl nanosuspension was prepared using antisolvent precipitation method, where Meclizine dissolved at room temperature in ethanol and emptied into water containing different stabilizer types (single and combined). The optimum formula (F4) was chosen based on particle size (295 nm), pdI (0.038), EE percent (97.9) and release profile (100 percent of drug release within 25 min) compared to the tablet navidoxine® on the market. In addition to the combination of stabilisers on particle size of drug nanosuspensions, the influence of formulation variables such as the type and concentration of stabilizer...

Objective: The objective of this study was to prepare floating gastric in situ gel of prochlorperazine maleate (PM) using nanoemulsion technology to improve drug solubility, bioavailability, reduce dosing frequency, and patient compliance. Methods: Eight nanoemulsion formulas (F1-F8) of PM were prepared by ultrasonication method using oil, surfactants: cosurfactants (Smix) with different types, concentrations, and ratios, and deionized distilled water. The nanoemulsion formulas were characterized to select the optimum recipe from which six floating in situ gel formulas (floating nanoemulsion in situ [FNI] 1-FNI 6) were prepared using sodium alginate as gelling agent, hydroxypropyl methylcellulose (HPMCK) 4M as rate retarding polymer, calcium chloride as cross-linking agent, calcium carbonate as floating agent, and sodium citrate as buffering and neutralizing gastric acid. All FNI formulas were subjected for the evaluation to assess the formulations suitability concerning the dosage form and intended therapeutic purpose. Results: Formulation variables such as the concentration of sodium alginate, HPMCK 4M, calcium carbonate, and calcium chloride affected the gelling properties, formulation viscosity, floating behavior, and in vitro drug release. Formulation FNI 6 showed acceptable floating lag time (55±2.3 s) and >12 h floating duration time, and observe prolong release of the drug in in-situ gelling preparation. Conclusion: The prepared FNI formulas of PM could float in the gastric conditions and released the drug in a sustained manner. The present formulation was enhanced drug solubility with good retention properties and better patient compliance.

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 ZofranP ® P 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 CR maxR and AUC R0-αR(P<0.001) with shorter TR max Rusing 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.

Objective: Oral nanoemulsion (NE) represent one of the newest technology to enhance intestinal drug permeability, bioavailability and facilitate swallowing of the oral dosage form. Methods: In this study, montelukast sodium (MS) nanoemulsions (NEs) were formulated by ultra-sonication using different surfactants (tween 20, tween 60 and tween 80) in different surfactant: co-surfactant (ethanol) ratios (Smix). The prepared NEs were evaluated for different parameters including droplet size (DS) using zetasizer as a function of ultra-sonication time, dispersibility, phase separation, conductivity, percent transmittance, optical transparency, in vitro release in addition to morphology using transmission electron microscopic (TEM). Results: The results revealed that F3 was the optimum formula having an average DS 32.95±2.8 nm after 5 min ultra-sonication assured by zetasizer and TEM, furthermore, a clear to bluish NE was formed after aqueous dilution with high conductivity (59.2±1.76 μs/cm) which indicated the formation of O/W NE. In addition, an optically clear NE was formed with (88.6±2.1) % transmittance with no sedimentation, creaming or separation after centrifugation signifying the formation of a stable NE. Finally, F3 showed faster dissolution rate (92.45%±1.66) after 30 min compared to other formulas. Conclusion: The net result of this study is the formulation of a stable oral NE containing MS which presents new easily swallowed dosage form that may enhance drug permeability as well as it may reduce drug metabolism leading to improving bioavailability for asthmatic patients.

Objective: Developing more effective and promising in situ gel nasal preparation for ondansetron HCl (OND-HCl) using nanoemulsion (NE) technology and study all the parameters that can optimize the final formula. Method: Screening of oils, surfactants and co-surfactants was performed on the basis of OND-HCl solubility and NE area of emulsifier ratio (Smix), respectively. Pseudo-ternary phase diagrams were constructed by aqueous titration method. Twelve NE formulas were prepared by ultrasonic emulsification and characterized for droplet size, zeta potential, polydispersity index, separation, conductivity, TEM, % transmittance, dilution and visual transparency. The best NE formulation was selected and applied to prepare nano-in situ gel (NIG) using poloxamer 407 as thermoreversible polymer, chitosan and HPMC E15 as mucoadhesive polymers. The six NIG formulas were evaluated for pH, drug content, osmolarity, gelation temperature, mucoadhesive force, viscosity and in vitro drug release. Results: The mean droplet size, polydispersity index, zeta potential, conductivity and % transmittance for the selected NE formula (F11) were found to be 64.87 nm, 0.544,-0.146, 210 μS/cm, and 99.08% respectively. The gelation temperatures, pH ,drug content, osmolarity and mucoadhesive force for the selected NIG formula (NIG6) were 33 ºC, 5.8, 99.215%, 106.06 mOsmol/l (0.62%), 7372.21 dyne/cm² respectively. The in vitro drug release study of NIG6 showed 100% after 6h. Conclusion: The results of this work indicated the possibility of application of NE technology in the formulation of NIG that has good mucoadhesive force to prolong the preparation residence time in the nose.

Pulsatile Drug Delivery Systems (PDDS) are getting considerable interest in delivering a drug at the correct position, at the correct time, and in the correct quantity, thus offering temporal, spatial, and intelligent delivery with improving patient compliance. These systems are intended to meet body's biological rhythm. Here, the delivery of drugs is assisted by the rhythm of disease. The main reason for the using pulsatile drug release is when the continuous drug release is not required. A PDDS must be designed in such a way that after the lag time a complete and fast release of drugs is achieved. The article deals with various systems such as osmotic system, capsular system, single and multi-unit system based on the utilization of erodible or soluble polymer coating and using of rupturable membrane. These systems are favorable to drugs with chronopharmacological behaviors such as drugs used to treat rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis. The current review paper focus on the causes for pulsatile drug delivery system design, types of illness requiring pulsatile release, classification, benefits, and restriction of this drug delivery system.

Objective: The current work was conducted with the aim of preparing rapidly dissolving strips of dexchlorpheniramine maleate to improve pediatric patient adherence for the best pharmaceutical reaction through the first-pass hepatic metabolism bypass. Methods: The oral strip was prepared using various polymers hydroxypropyl methylcellulose (HPMC E15, HPMC K4M, and polyvinyl alcohol) using solvent casting methodology. Various types of plasticizers polyethylene glycol (PEG 400 and propylene glycol) have been used to raise the features of the strip preparation polymer. Results: From this work, formula 3, consisting of 360 mg HPMC E15 as a polymer and 1 ml PEG 400 as a plasticizer, offers acceptable formulation characteristics and rapid drug release (100%) at 10 min compared to the Polaramine®(Schering-Plough) tablets (66.18%) on the market. Conclusion: The optimum formula (F3) has been chosen to prepare rapidly dissolving strips to be useful for pediatric drug dosage by offering quicker release and better patient compliance. KEY WORDS: Hydroxypropyl methylcellulose E15, Pediatric, Polyethylene glycol 400, Strip