Assessment of Binary Agarose-Carbopol Buccal Gels for Mucoadhesive Drug Delivery: Ex Vivo and In Vivo Characterization.

Agarose (AG) is a naturally occurring biocompatible marine seaweed extract that is converted to hydrocolloid gel in hot water with notable gel strength. Currently, its mucoadhesion properties have not been fully explored. Therefore, the main aim of this study was to evaluate the mucoadhesive potential of AG binary dispersions in combination with Carbopol 934P (CP) as mucoadhesive gel preparations. The gels fabricated via homogenization were evaluated for ex vivo mucoadhesion, swelling index (SI), dissolution and stability studies. The mucoadhesive properties of AG were concentration dependent and it was improved by the addition of CP. Maximum mucoadhesive strength (MS) (27.03 g), mucoadhesive flow time (FT) (192.2 min), mucoadhesive time in volunteers (MT) (203.2 min) and SI (23.6% at 4 h) were observed with formulation F9. The mucoadhesive time investigated in volunteers (MT) was influenced by AG concentration and was greater than corresponding FT values. Formulations containing 0.3%, w/v AG (F3 and F9) were able to sustain the release (~99%) for both drugs till 3 h. The optimized formulation (F9) did not evoke any inflammation, irritation or pain in the buccal cavity of healthy volunteers and was also stable up to 6 months. Therefore, AG could be considered a natural and potential polymer with profound mucoadhesive properties to deliver drugs through the mucosal route.

Fixed Dose Single Tablet Formulation with Differential Release of Amlodipine Besylate and Simvastatin and Its Pharmacokinetic Profile: QbD and Risk Assessment Approach.

PURPOSE: A differential release fixed dose matrix tablet of amlodipine besylate (AML-B) and simvastatin (SIM) was formulated to enhance patient compliance. MATERIAL AND METHOD: In the first phase, release controlling parameters of AML-B and SIM granules were identified and in the second phase a fixed dose AML-B and SIM tablet formulation was prepared and optimized for a differential release of the drugs using a quality by design (QbD) and risk assessment approach. A validated HPLC method was employed for simultaneous determination of AML-B and SIM for FDC formulation. A pharmacokinetics of the above drugs was studied in healthy dogs in the third phase. RESULTS: In QbD-based optimized formulation, Eudragit® RSPO-dicalcium phosphate (DCP) blend controlled the release of AML-B over 8 h, though this diffusion-controlled release assumed first order kinetics. DCP and Eudragit® RS 100 also retarded release of SIM causing SIM release over 8 h after AML-B release from the optimized FDC tablet formulation. The HPLC retention times of AML-B and SIM were 2.10 and 15.52 min, respectively. Linearity for AML-B was 5.0-50 ng/mL and 0.01-2.0 µg/mL for SIM with percent recoveries of 92.85-101.53% and 94.51-117.75% for AML-B and SIM. AUC0-∞ of AML-B was increased 3 fold, while AUC0-∞ of SIM was decreased 2 fold. The tmax values for AML-B and SIM were 12 and 6 h, respectively. AML-B was absorbed without any lag time (tlag) while tlag was 6.33 ± 0.81 h for SIM, thus met the study objective. CONCLUSION: The pharmacokinetic study showed an immediate absorption of AML-B while that of SIM was withheld for 6 h, close to the desired delay time of 8 h.

Nexus between urbanization, emission, openness, and energy intensity: panel study across income groups.

Energy is a basic need for the fulfillment of human activities, and usage of energy causes a rise in the carbon emission levels. This paper examines the impact of trade openness, urbanization, imports and exports on carbon emission, and energy intensity for 192 countries from higher, upper-middle, lower-middle, and low-income groups. The data are taken from the year 1990 to 2017 and Generalized method of moments (GMM) is applied for the empirical analyses. Results showed that energy use has less impact on carbon emission in high-income and lower-middle-income economies as compared to the other three sub-panels. Likewise, as a whole, urbanization showed inverse association with emission, on the other hand, it showed positive association with energy intensity in the high-income group. Trade openness showed a positive and highly significant influence on emission as well as on energy intensity. Exports and imports exposed different relations with carbon emission and energy intensity. Outcomes of a Granger causality test yielded an indication of varied causality associations between the variables across the income-based sub-panels. The study suggested the need for improvement in technologies and facilities across the countries for the decline of carbon emission and the enhancement of energy intensity.

Access to medicines - a systematic review of the literature.

BACKGROUND: Budgetary constraints and the rising cost of new innovative medicines are the key challenges for access to medicines. Multiple research studies explored diverse dimensions of this topic, however, a thorough and detailed review of existing literature on access to medicines in United Kingdom is lacking. Therefore, the objective of this systematic review of literature was to critically review and analyse the literature pertaining to original research on access to medicines issue in the United Kingdom. This review includes two types of studies: (a) UK centric studies (b) studies comparing UK with the other countries. METHODS: A systematic search of articles published between Jan 2008 and October 12, 2018 was conducted according to PRISMA guidelines using the following databases: PubMed, Scopus, Science Direct, and specific journals including BMJ, Lancet, Value in Health, Pharmacoeconomics, Pharmacoeconomics Open, Journal of pharmaceutical policy and practice, Health Policy. RESULTS: The searches across all databases and journals resulted in 53 relevant articles. The data extracted from the 53 articles generated key themes. These themes included: Access to Medicines, Health technology assessment (HTA), Pricing and Health technology assessment, Risk Sharing Agreements & Stakeholders involvement/views on reimbursement Process. Subthemes were added under the key themes where applicable. CONCLUSIONS: This review systematically evaluated the current literature and identified variability in access to medicines across countries in UK &EU and across different categories of medicines. Medicine licensing and reimbursement environment is continuously evolving and there are challenges as well as opportunities for learning and collaboration among countries which are at different stages of advancement in their systems.

Characterization of inheritance and preliminary biochemical mechanisms of spirotetramat resistance in Phenacoccus solenopsis Tinsley: An economic pest from Pakistan.

Phenacoccus solenopsis is an economically important insect pest of different agronomic and horticultural field crops. In Pakistan, the cotton crop was severely attacked by P. solenopsis during 2007 and since then a varied group of insecticides are used by farmers to manage this pest. As a result, insecticide resistance has become a barrier in control of P. solenopsis. The current study was designed to explore the basics of genetics, realized heritability and possible genetic mechanisms of resistance against spirotetramat in P. solenopsis. Before selection, the wild population (Wild-Pop) showed 5.97-fold resistance when compared with lab-reared susceptible strain (Susceptible Lab-Pop). The P. solenopsis was selected with spirotetramat to 21 generations, called Spiro-SEL Pop, which showed 463.21-fold resistance as compared with the Susceptible Lab-Pop. The values of LC50 for F1 (Spiro-SEL Pop ♂ × Susceptible Lab-Pop ♀) and F1 (Spiro-SEL Pop ♀ × Susceptible Lab-Pop ♂) populations were statistically similar and values of dominance level were 0.42 and 0.54, respectively. Reciprocal crosses between Susceptible Lab-Pop and Spiro-SEL Pop showed that resistance was of autosomal in nature with incomplete dominant traits. According to the fit test, monogenic model estimation of the number of genes, which are responsible for the development of spirotetramat resistance in a population of P. solenopsis, showed that multiple genes are involved in controlling the resistance levels in tested strains of P. solenopsis. The value of heritability for resistance against spirotetramat was 0.13 in P. solenopsis. Our results suggested the presence of a metabolic-based resistance mechanism associated with the monooxygenases in P. solenopsis, while testing the synergism mechanism. These results will provide the baseline to design an effective control strategy to manage P. solenopsis in the field.