Cutaneous Pharmacokinetics of Topically Applied Novel Dermatological Formulations.

Novel formulations are developed for dermatological applications to address a wide range of patient needs and therapeutic challenges. By pushing the limits of pharmaceutical technology, these formulations strive to provide safer, more effective, and patient-friendly solutions for dermatological concerns, ultimately improving the overall quality of dermatological care. The article explores the different types of novel dermatological formulations, including nanocarriers, transdermal patches, microsponges, and microneedles, and the techniques involved in the cutaneous pharmacokinetics of these innovative formulations. Furthermore, the significance of knowing cutaneous pharmacokinetics and the difficulties faced during pharmacokinetic assessment have been emphasized. The article examines all the methods employed for the pharmacokinetic evaluation of novel dermatological formulations. In addition to a concise overview of earlier techniques, discussions on novel methodologies, including tape stripping, in vitro permeation testing, cutaneous microdialysis, confocal Raman microscopy, and matrix-assisted laser desorption/ionization mass spectrometry have been conducted. Emerging technologies like the use of microfluidic devices for skin absorption studies and computational models for predicting drug pharmacokinetics have also been discussed. This article serves as a valuable resource for researchers, scientists, and pharmaceutical professionals determined to enhance the development and understanding of novel dermatological drug products and the complex dynamics of cutaneous pharmacokinetics.

Susceptibility Loci for Type 2 Diabetes in the Ethnically Endogamous Indian Sindhi Population: A Pooled Blood Genome-Wide Association Study.

Type 2 diabetes (T2D) is a complex metabolic derangement that has a strong genetic basis. There is substantial population-specificity in the association of genetic variants with T2D. The Indian urban Sindhi population is at a high risk of T2D. The genetic basis of T2D in this population is unknown. We interrogated 28 pooled whole blood genomes of 1402 participants from the Diabetes In Sindhi Families In Nagpur (DISFIN) study using Illumina's Global Screening Array. From a total of 608,550 biallelic variants, 140 were significantly associated with T2D after adjusting for comorbidities, batch effects, pooling error, kinship status and pooling variation in a random effects multivariable logistic regression framework. Of the 102 well-characterized genes that these variants mapped onto, 70 genes have been previously reported to be associated with T2D to varying degrees with known functional relevance. Excluding open reading frames, intergenic non-coding elements and pseudogenes, our study identified 22 novel candidate genes in the Sindhi population studied. Our study thus points to the potential, interesting candidate genes associated with T2D in an ethnically endogamous population. These candidate genes need to be fully investigated in future studies.

Effect of an education-based workplace intervention (move in office with education) on sedentary behaviour and well-being in desk-based workers: a cluster randomized controlled trial.

This study aimed to assess the effectiveness of short-term workplace-based physical activity education on altering sitting outcomes, maximal oxygen consumption (VO2max) and occupational well-being. Four office clusters (46 participants) of desk-based workers were randomized to either the move in office with education (MOWE) group or the control (CONT) group for 4 weeks. The outcomes were occupational sedentary time, VO2max and workplace well-being. Data were analysed using non-parametric tests. Our study results did not show any significant change in sitting time or VO2max. Nevertheless, workplace well-being of the MOWE group significantly improved when compared to the CONT group, especially in the domains of work satisfaction (odds ratio 11.67; p = 0.001) and employer care (odds ratio 0.167; p = 0.001). Workplace education (MOWE) improves well-being but may not alter sitting outcomes or VO2max in office workers. Workplace education without policy change may not yield positive health outcomes.

Genetic association of anthropometric traits with type 2 diabetes in ethnically endogamous Sindhi families.

BACKGROUND: Ethnically endogamous populations can shed light on the genetics of type 2 diabetes. Such studies are lacking in India. We conducted this study to determine the genetic and environmental contributions of anthropometric traits to type 2 diabetes risk in the Sindhi families in central India. METHODS: We conducted a family study in Indian Sindhi families with at least one case of type 2 diabetes. Variance components methods were used to quantify the genetic association of 18 anthropometric traits with eight type 2 diabetes related traits. Univariate and bivariate polygenic models were used to determine the heritability, genetic and environmental correlation of anthropometric traits with type 2 diabetes related traits. RESULTS: We included 1,152 individuals from 112 phenotyped families. The ascertainment-bias corrected prevalence of type 2 diabetes was 35%. Waist circumference, hip circumference and the biceps, triceps, subscapular and medial calf skinfold thicknesses were polygenically and significantly associated with type 2 diabetes. The range of heritability of the anthropometric traits and type 2 diabetes related traits was 0.27-0.73 and 0.00-0.39, respectively. Heritability of type 2 diabetes as a discrete trait was 0.35. Heritability curves demonstrated a substantial local influence of type 2 diabetes related traits. Bivariate trait analyses showed that biceps and abdominal skinfold thickness and all waist-containing indexes were strongly genetically correlated with type 2 diabetes. CONCLUSIONS: In this first study of Sindhi families, we found evidence for genetic and environmental concordance of anthropometric traits with type 2 diabetes. Future studies need to probe into the genetics of type 2 diabetes in this population.

Melt Dispersion Adsorbed onto Porous Carriers: An Effective Method to Enhance the Dissolution and Flow Properties of Raloxifene Hydrochloride.

The objective of the present investigation is to enhance the dissolution and flow properties of raloxifene hydrochloride (RXH), a biopharmaceutical classification system class II drug. Melt dispersion of RXH with polyethylene glycol (PEG) 6000 was prepared by the fusion method. The melt dispersion was then adsorbed onto a porous adsorbent, Neusilin, by the melt adsorption method. Response surface methodology was employed to establish the design space for formulation variables such as the ratio of RXH to PEG 6000 in melt dispersion and amount of porous adsorbent to melt dispersion. Differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and accelerated stability techniques were utilized to characterize formulations. Negative Gibbs free energy values indicated spontaneous solubilization of RXH in PEG 6000. The time required for 80% of drug release from optimized formulation was <20 min compared with plain RXH. Accelerated stability studies confirmed the stabilization of amorphous melt dispersion in nanopores (nanoconfinement) of inorganic silicate Neusilin. Melt dispersion, adsorbed on porous carriers, is a promising technique to improve the dissolution characteristic as well as flow properties of drug molecules.

Spray dried solid dispersion of repaglinide using hypromellose acetate succinate: in vitro and in vivo characterization.

OBJECTIVE: This research study attempted to develop spray-dried solid dispersion, to enhance the solubility of repaglinide, an antidiabetic drug. SIGNIFICANCE: Aqueous solubility plays a major role in drug delivery because any chemical entity has to be in a dissolved state at the site of absorption, in order to get absorbed. Solid dispersion (SD) is one of the widely used techniques to enhance solubility and hence dissolution rate of poorly soluble drugs. METHODS: Repagnilide, in hypromellose acetate succinate (HPMCAS) solution, was dried by spray drying to obtain spray-dried solid dispersion (SDSD). Plackett-Burman and Box-Behnken designs were used for screening formulation as well as process parameters, and optimization respectively. DSC, XRD, SEM were carried out to confirm the preparation of solid dispersion. SDSD was evaluated for in vitro dissolution, flow properties, Percentage yield and in vivo oral glucose tolerance test. RESULT: Spray dried solid dispersion comprising (w/w) drug:polymer ratio of 1:3.82, 2.56% of aerosil and inlet temperature of 90 °C, corresponded to the best formulation obtained in this work. It showed t 85% of less than 15 min and a significant reduction in blood glucose level in rats as compared to pure drug and marketed formulation. CONCLUSION: Thus, it can be concluded that spray-dried solid dispersion prepared using HPMCAS is a useful technique for solubility and dissolution enhancement of repaglinide.