Floating granules of ranitidine hydrochloride-gelucire 43/01: Formulation optimization using factorial design

The purpose of this research was to develop and optimize a controlled-release multiunit floating system of a highly water soluble drug, ranitidine HCl, using Compritol, Gelucire 50/13, and Gelucire 43/01 as lipid carriers. Ranitidine HCl-lipid granules were prepared by the melt granulation technique and evaluated for in vitro floating and drug release. ethyl cellulose, methylcellulose, and hydroxypropyl methylcellulose were evaluated as release rate modifiers. A 32 full factorial design was used for optimization by taking the amounts of Gelucire 43/01 (X1) and ethyl cellulose (X2) as independent variables, and the percentage drug released in 1(Q1), 5(Q5), and 10 (Q10) hours as dependent variables. The results revealed that the moderate amount of Gelucire 43/01 and ethyl cellulose provides desired release of ranitidine hydrochloride from a floating system. Batch F4 was considered optimum since it contained less Gelucire and was more similar to the theoretically predicted dissolution profile (f2=62.43). The temperature sensitivity studies for the prepared formulations at 40°C/75% relative humidity for 3 months showed no significant change in in vitro drug release pattern. These studies indicate that the hydrophobic lipid Gelucire 43/01 can be considered an effective carrier for design of a multiunit floating drug delivery system for highly water soluble drugs such as ranitidine HCl

In vitro test to evaluate the interaction between synthetic cervical mucus and vaginal formulations

The interaction and mixing between a bilayer sample of mucus and vaginal formulation was evaluated through viscosity measurements with respect to time and shear. Physical mixtures of mucus and vaginal formulation were used as controls. Three test protocols were designed: (1) constant shear, (2) intermittent shear, and (3) delayed shear. Several marketed vaginal products (Gynol II, KY Plus, KY, and Advantage-S) and experimental formulations (C31G with hydroxyethylcellulose [HEC]) were evaluated and compared by these tests. The results of the constant shear test showed that the shear stress profile of the bilayer approached that of the corresponding physical mixture, consistent with complete mixing of the bilayer under shear. The time taken for the bilayer to mix completely was in the following order: KY Plus > Gynol II and C31G > KY > Advantage-S. Under the intermittent shear protocol, the following order for complete mixing was observed: KY Plus > C31G > Gynol II > KY > Advantage-S. The 2 products evaluated by the delayed shear test, C31G and Gynol II, were both completely mixed at 180 minutes. The development of an in vitro test, when coupled with in vivo data, should serve in the screening and evaluation of future vaginal formulations

General anaesthesia versus local anaesthesia for carotid surgery (GALA): a multicentre, randomised controlled trial

BACKGROUND: The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia. METHODS: We undertook a parallel group, multicentre, randomised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries. Participants were randomly assigned to surgery under general (n=1753) or local (n=1773) anaesthesia between June, 1999 and October, 2007. The primary outcome was the proportion of patients with stroke (including retinal infarction), myocardial infarction, or death between randomisation and 30 days after surgery. Analysis was by intention to treat. The trial is registered with Current Control Trials number ISRCTN00525237. FINDINGS: A primary outcome occurred in 84 (4.8%) patients assigned to surgery under general anaesthesia and 80 (4.5%) of those assigned to surgery under local anaesthesia; three events per 1000 treated were prevented with local anaesthesia (95% CI -11 to 17; risk ratio [RR] 0.94 [95% CI 0.70 to 1.27]). The two groups did not significantly differ for quality of life, length of hospital stay, or the primary outcome in the prespecified subgroups of age, contralateral carotid occlusion, and baseline surgical risk. INTERPRETATION: We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery. The anaesthetist and surgeon, in consultation with the patient, should decide which anaesthetic technique to use on an individual basis. FUNDING: The Health Foundation (UK) and European Society of Vascular Surgery