Development and evaluation of liquid oral controlled release systems for Losartan potassium

Losartan potassium is a water soluble antihypertensive agent with short half-life. Controlling its release will improvepatient compliance. The benefit will be extended for geriatric patients if the developed system was liquid. The objectiveof this work was to develop controlled release oral liquid losartan potassium. This employed a combination of in situgelation and coating drug particles with pH-dependent polymer (Eudragit® L100). Solid dispersion (SD) prepared at1:1, 1:1.5, and 1:2 drug : polymer ratios, respectively. Sodium alginate solution was loaded with either pure drug orSD, in presence and absence of 1% w/v chitosan. These systems were evaluated for the drug release using continuouspH variation study. Alginate formulation with pure drug underwent in situ gelation in the gastric conditions but lost thegelling strength in the intestinal phase with burst drug release. Loading the formulation with SD resulted in controlleddrug release both in the gastric and intestinal phases. Increasing eudragit concentration in SD decreased the drugreleased with total release efficiency of 62.1%, 53.0%, and 41.7%. Incorporation of chitosan at reduced further drugrelease rate reaching 21% at the higher eudragit concentration. The study provided the formulator with a range of oralliquid formulations for controlled release of losartan potassium.

Natural and synthetic oil phase transition microemulsions for ocular delivery of tropicamide: efficacy and safety.

The objective of this work was to investigate the efficacy and safety of natural oils (castor oil and olive oil) based phase transition microemulsion systems for ocular delivery with reference to ethyl oleate systems. Tropicamide was used as model drug and was incorporated in the formulation at a concentration of 0.5% w/w. The phase transition systems comprised the oil, surfactant and water with the phase behavior depending on the concentration of water. The tested systems included microemulsion (ME), liquid crystalline system (LC) and coarse emulsion (EM). The efficacy of these systems was evaluated by monitoring the mydriatic response in comparison to drug solution containing polyvinylpyrrolidone (PVP). Ocular irritation was monitored by visual inspection and tear flow estimation. Drug release depended on the formulation type and viscosity. Thus LC systems produced the slowest release rates followed by the ME with the EM producing the largest release rate. The mydriatic response versus time plots showed biphasic effect with two maxima (MRmax) which verified the systemic absorption of the drug. Both ethyl oleate and olive oil based systems were more effective than the control with respect to the area under the mydriatic response profile. However, castor oil based systems were comparable to the control. With respect to ocular irritation castor oil based system were the least irritant followed by olive oil systems with ethyl oleate systems being the most irritant. The study thus introduced olive oil based phase transition systems for ocular drug delivery with lower irritation compared to the synthetic oil systems.

Optimization of the entrapment efficiency and release of ambroxol hydrochloride alginate beads.

The objective of the current study was to optimize the composition of alginate beads to produce ambroxol hydrochloride alginate beads with optimum specifications. The study employed beads based on sodium alginate solution (2% w/v) as the main component with calcium chloride solution as crosslinking agent as the prototype beads. The beads were prepared by syringe method. The effect of viscosity modifiers on the morphology, entrapment efficiency and drug release was studied. The prototype beads were spherical semitransparent with entrapment efficiency (EE) of 23%. Incorporation of polyvinylpyrrolidone (PVP) as a viscosity modifier produced spherical semitransparent beads with higher EE values compared with the prototype. Addition of carboxymethyl cellulose (CMC) produced oval opaque beads which have larger size and higher EE values compared with the prototype beads or those containing PVP only. Replacement of CMC with hydroxypropyl methyl cellulose (HPMC) produced semitransparent spherical beads with significant increase in the EE. Monitoring the drug release rate from different beads, the all the tested beads were able to retain the drug in the stomach condition. In the intestinal conditions the release rate depended on the composition of the beads with prototype beads librating most of its contents in the first 15 minutes. Formulations containing either CMC or HPMC were able to retard the drug release in the intestinal phase. In conclusion the study developed beads with optimum entrapment and release of ambroxol hydrochloride.

Skin delivery of nisoldipine from niosome proconcentrate.

Nisoldipine is used for treatment of hypertension and angina pectoris. However, it suffers from very low bioavailability due to its extensive pre-systemic metabolism. This together with its low dose made it excellent candidate for transdermal delivery. Accordingly, the aim of this study was to develop and evaluate transdermal delivery system for optimization of nisoldipine skin permeability. Proniosomes comprising cholesterol and span 60 with different ratios together with ethanol and minimal water were evaluated for such aim. The developed formulations were assessed with respect to drug entrapment efficiency, viscosity, in vitro drug release and transdermal permeability. All proniosomal formulations have significantly enhanced transdermal delivery of nisoldipine compared with saturated aqueous solution of the drug. Increasing cholesterol content resulted in reduced drug flux. The study was extended to compare the efficacy of such proniosomes to the corresponding niosomes. Proniosomes significantly optimized transdermal delivery of nisoldipine compared to their hydrated form. Such results contradict the hypothesis which claimed the necessity for niosome formation from proniosomes for efficient transdermal delivery with penetration enhancement being mainly responsible for improved delivery.