Effect of Permeation Enhancers on the Release Behavior and Permeation Kinetics of Novel Tramadol Lotions

Purpose: The aim of this research work was to formulate, characterize and evaluate the in vitro permeation behavior of tramadol lotion containing propylene glycol (PG) and polyethylene glycol (PEG) as permeation enhancers.Methods: The permeation experiments were conducted in vitro using full thickness rabbit skin in Franz diffusion cells. The donor compartment was filled with PBS (phosphate buffered saline) at pH 7.4 ± 0.1. The receptor phase was continuously stirred PBS (pH 7.4) at 37 °C ± 0.5. The amount of tramadol permeated into the receptor phase was determined spectrophotometrically at 271 nm. Various permeation parameters such as permeation coefficient (Kp), diffusion coefficient (D), flux (J), input rate,and enhancement ratio were obtained using Fick’s diffusion laws.Results: Permeation increased with increase in the concentrations of both enhancers tested. Maximum cumulative amount permeated for control lotion (Lc) was 357 ìg/cm2/min with input rate 0.574 ìg/min and lag time (tlag) of 34.93 min, while for the optimum test lotion (L4, containing 8 % PG/PEG in ratio of 1:1 v/v), it was 926 ìg/cm2/min, 1.482 ìg/min and 58.36 min, respectively. The significantly (p < 0.05) higher permeability shown by the test lotion L4 can be attributed, in part, to the interaction of PG withintercellular lipids leading to the disruption of their organization and increasing their fluidity, and also partly as a result of solubilization of lipid bilayers by PEG.Conclusion: A binary system of PG and PEG in lotion can be successfully utilized for the permeation enhancement of tramadol.Keyword: Tramadol, Transdermal delivery, Permeation, Propylene glycol, Polyethylene glycol, Rabbit skin

Formulation and Permeation Kinetic Studies of Flurbiprofen Gel

Purpose: To investigate the in vitro permeation and drug release kinetics of flurbiprofen gel.Methods: Thirteen batches (G1, G2 … G13) of flurbiprofen gels were prepared using different ratios ofpermeation enhancers, i.e., propylene glycol (PG) and polyethylene glycol (PEG), by response surface methodology (RSM). Viscosity, pH, spreadability, consistency and drug content of the flurbiprofen gels were measured. Permeation experiments were conducted using silicone membrane in a modified Franz diffusion cell. Permeation parameters determined include diffusion coefficient (D), Flux (J), lag time (tLag), permeation coefficient (Kp), input rate (IR) and enhancement ratio (ER). Primary skin irritation test was performed for the optimized gel, G3, using 11 human volunteers.Results: Maximum solubility (72.15 ± 0.02 mg/mL) of flurbiprofen was observed in a mixture (2:1) of methanol and water. Partition coefficient (Ko/w) was determined as logP = 3.68 ± 0.11. The gels were stable under various storage conditions, and were homogenous, crystalline and transparent. Viscosity, pH, spreadability, consistency and drug content were in the range of 150 – 178 × 102 cps, 5.42 - 5.75, 5.0 - 7.0 g.cm/s, 3.0 - 9.0 mm, and 97.99 - 99.86 %, respectively. No irritation or lesions (erythma, redness and ulceration) occurred in human volunteers over a 30-day period. The optimized formulation, G3, showed maximum flux through silicone membrane.Conclusion: PG and PEG are effective enhancers of flurbiprofen from  various formulations when used in various ratios.Keywords: Flurbiprofen, Gel, Diffusion, Permeation enhancers, Skin irritation, Silicone membran

Quality of medication use in primary care - mapping the problem, working to a solution: a systematic review of the literature

Background: The UK, USA and the World Health Organization have identified improved patient safety in healthcare as a priority. Medication error has been identified as one of the most frequent forms of medical error and is associated with significant medical harm. Errors are the result of the systems that produce them. In industrial settings, a range of systematic techniques have been designed to reduce error and waste. The first stage of these processes is to map out the whole system and its reliability at each stage. However, to date, studies of medication error and solutions have concentrated on individual parts of the whole system. In this paper we wished to conduct a systematic review of the literature, in order to map out the medication system with its associated errors and failures in quality, to assess the strength of the evidence and to use approaches from quality management to identify ways in which the system could be made safer. Methods: We mapped out the medicines management system in primary care in the UK. We conducted a systematic literature review in order to refine our map of the system and to establish the quality of the research and reliability of the system. Results: The map demonstrated that the proportion of errors in the management system for medicines in primary care is very high. Several stages of the process had error rates of 50% or more: repeat prescribing reviews, interface prescribing and communication and patient adherence. When including the efficacy of the medicine in the system, the available evidence suggested that only between 4% and 21% of patients achieved the optimum benefit from their medication. Whilst there were some limitations in the evidence base, including the error rate measurement and the sampling strategies employed, there was sufficient information to indicate the ways in which the system could be improved, using management approaches. The first step to improving the overall quality would be routine monitoring of adherence, clinical effectiveness and hospital admissions. Conclusion: By adopting the whole system approach from a management perspective we have found where failures in quality occur in medication use in primary care in the UK, and where weaknesses occur in the associated evidence base. Quality management approaches have allowed us to develop a coherent change and research agenda in order to tackle these, so far, fairly intractable problems

An unbiased lipid phenotyping approach to study the genetic determinants of lipids and their association with coronary heart disease risk factors

Direct infusion high-resolution mass spectrometry (DIHRMS) is a novel, high-throughput approach to rapidly and accurately profile hundreds of lipids in human serum without prior chromatography, facilitating in-depth lipid phenotyping for large epidemiological studies to reveal the detailed associations of individual lipids with coronary heart disease (CHD) risk factors. Intact lipid profiling by DIHRMS was performed on 5662 serum samples from healthy participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS). We developed a novel semi-targeted peak-picking algorithm to detect mass-to-charge ratios in positive and negative ionization modes. We analyzed lipid partial correlations, assessed the association of lipid principal components with established CHD risk factors and genetic variants, and examined differences between lipids for a common genetic polymorphism. The DIHRMS method provided information on 360 lipids (including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids), with a median coefficient of variation of 11.6% (range: 5.4–51.9). The lipids were highly correlated and exhibited a range of associations with clinical chemistry biomarkers and lifestyle factors. This platform can provide many novel insights into the effects of physiology and lifestyle on lipid metabolism, genetic determinants of lipids, and the relationship between individual lipids and CHD risk factors