Formulation of sumatriptan succinate orodispersible tablets using chitosan and sodium starch glycolate for immediate migraine relief.

Migraine is one of the common neurological disease affecting around 23% of the Pakistani population. Prompt treatment is required to regain the functional ability of patients. The present study was designed to develop sumatriptan succinate orodispersible tablets that would quickly overcome acute migraine episodes using 22 full-factorial design. The chitosan and sodium starch glycolate were taken as independent variables; friability, disintegration, dispersion time and water absorption ratio as response variables. Eight trial formulations were generated by Design Expert® software. The main effect plots were used to check the interaction of formulations with response variables. All trial formulations showed good micromeritic properties in terms of angle of repose (19.59o-24.57°), Carr's index (17.08-24.90%) and Hausner's ratio (1.20-1.33). The tablets wetted quickly (17.1- 39 sec) in dispersion medium, showed higher water absorption ratio (188-341 sec) and disintegrated quickly (13-20 sec) with an excellent dissolution rate (94-99%). The main effect plots show interactions between the independent variables against most of the study responses. A 22 full-factorial model was found to be effective in studying the influence of formulation variables on response parameters. Both chitosan and sodium starch glycolate can be used in combination to fabricate an effective orodispersible formulation of sumatriptan succinate.

The pathological role of C-X-C chemokine receptor type 4 (CXCR4) in colorectal cancer (CRC) progression; special focus on molecular mechanisms and possible therapeutics.

Colorectal cancer (CRC) is comprised of transformed cells and non-malignant cells including cancer-associated fibroblasts (CAF), endothelial vasculature cells, and tumor-infiltrating cells. These nonmalignant cells, as well as soluble factors (e.g., cytokines), and the extracellular matrix (ECM), form the tumor microenvironment (TME). In general, the cancer cells and their surrounding TME can crosstalk by direct cell-to-cell contact and via soluble factors, such as cytokines (e.g., chemokines). TME not only promotes cancer progression through growth-promoting cytokines but also provides resistance to chemotherapy. Understanding the mechanisms of tumor growth and progression and the roles of chemokines in CRC will likely suggest new therapeutic targets. In this line, a plethora of reports has evidenced the critical role of chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine ligand 12 (CXCL12 or SDF-1) axis in CRC pathogenesis. In the current review, we take a glimpse into the role of the CXCR4/CXCL12 axis in CRC growth, metastasis, angiogenesis, drug resistance, and immune escape. Also, a summary of recent reports concerning targeting CXCR4/CXCL12 axis for CRC management and therapy has been delivered.

Influence of Prunus domestica gum on the release profiles of propranolol HCl floating tablets.

Propranolol hydrochloride is a beta-blocker used for the management and treatment of hypertension, angina, coronary artery disease, heart failure, fibrillation, tremors, migraine etc. The objective of the present study was to design Propranolol Hydrochloride floating tablets by direct compression method and to explore the role of a new gum as a matrix former. A 22 full factorial design was selected for the present study. Prunus domestica gum and HPMC (K4M) were used as independent variables, swelling index and drug dissolution at 12 hours as dependent variables. Formulations were subjected to pre- and post-compression tests that showed good micromeritics and buoyancy characteristics (Carr's index 11.76%-14.00%, Hausner's ratio 1.13°-1.16°, angle of repose 22.67°-25.21°, floating lag time 56-76 seconds, total floating time 18-25 hours and swelling index 59.87%-139.66%). The cumulative drug release in 0.1 N HCl at 12 hours was 72%-90% (p<0.05). Weibull model was found to be the best fit model (R2>0.99) among all other studied models. Multiple regression showed a significant effect of Prunus domestica gum and HPMC K4M on the swelling index and dissolution profiles of propranolol HCl (p<0.05). On the basis of better in-vitro performance and cost-effectiveness, formulation F4 was the best formulation. It is evident from the results that Prunus domestica gum possesses excellent drug release retardant potential for the floating drug delivery system and this new gum should be further explored alone or with other natural and synthetic polymers in future studies.

Mini right axillary thoracotomy for congenital heart defect repair can become a safe surgical routine.

OBJECTIVE: Owing to its obvious cosmetic appeal, minimal invasive repair of congenital heart defects (CHDs) through the mini right axillary thoracotomy is becoming routine in many centres. Besides cosmesis, and before becoming a new norm, it is important to establish its outcomes as safe compared to repairs through traditional median sternotomy. METHODS: Between 2013 and 2021, 116 consecutive patients underwent defect repairs through mini right axillary thoracotomy. Patient, operative data, and hospital outcomes were compared to contemporary mini right axillary thoracotomy and sternotomy series. RESULTS: There was no mortality or need for approach conversion (mean age 4.3 years, range 0.17-17, mean weight 18.6 kg, range 4.8-74.4) in 118 repairs for atrial septal defect, ventricular septal defect, partial anomalous pulmonary venous return, partial atrioventricular canal with mitral cleft, scimitar syndrome, double-chambered right ventricle, cor triatriatum, and tricuspid valve repair. Protocol included on-table extubation, achieved in 97 children, with 23 outliers leading to 0.7 average hours of mechanical ventilation (range 0-66 hours), indwelling chest drain time of 2.6 days (range 1-9 days), intensive care stay of 1.8 days (range 1-10 days), and hospital stay of 3.9 days (range 2-18 days). Late revisions were required in one patient after scimitar repair for scimitar vein stenosis at 2 weeks, and in another for repair of superior caval vein stenosis after a Warden operation at 2 months; reoperations (5/116 = 4.3%) were successfully performed through the same mini right axillary incision. CONCLUSIONS: While providing obvious cosmetic advantages, the minimally invasive right axillary thoracotomy approach for the surgical repair of common CHDs yields excellent results and is safe compared to the benchmark median sternotomy approach.

Possibility of extending biopharmaceutics classification system based biowaiver to BCS class IIa drug.

Biowaiver studies have been performed to assess the bioequivalence of two drug products. Ibuprofen is a Biopharmaceutics Classification System (BCS) class IIa drug (Low solubility - High permeability) used as analgesic, antipyretic and anti-inflammatory agent. World Health Organization (WHO) placed ibuprofen in the category of biowaiver drugs but Food and drug authority (FDA) and International Council for Harmonization (ICH) has not issued yet any guidelines regarding the biowaiver of BCS class II drugs. Present study was aimed to formulate immediate release (IR) Ibuprofen 600 mg tablets with variable disintegrants. All trial film coated formulations were evaluated physicochemically with in-vitro bioequivalence studies in three buffer mediums (pH 6.8, pH 4.5 and pH 1.2). Samples were analyzed spectrophotometrically at 221 nm and model independent approaches (dissimilarity (f1), similarity (f2;) and Boot strap) was applied to assess the observed similarity. The similarity factor (f2;) was achieved only in pH 1.2 in three trial formulations and met acceptance criteria (f2; 50-100) although the amount of drug release was negligible. This investigation revealed that for BCS class IIa drug (ibuprofen), subsequent analysis of excipients used, pKa of drug and method of manufacturing should also be considered to ensure bioequivalence for a successful biowaiver study.

Promoting Higher Quality of Care Through Education of Pediatric Residents on the Medical Home Model.

The objective of this project was to present educational modules to pediatric residents and to assess if the modules improved residents' understanding of the patient- and family-centered medical home model. Eighteen residents participated in 3 separate training sessions taught by fellow residents, which covered a total of 5 modules. Pretests and posttests were administered for each module. All modules showed improved scores from pretest to posttest, but only one module showed statistically significant improvement. The modules also incorporated discussion sessions that led to clinical practice change. These results revealed that resident-administered education using predeveloped modules can be effective in increasing knowledge related to the medical home model and in changing resident clinical practice.

The morpho-agronomic characterization study of Lens culinaris germplasm under salt marsh habitat in Swat, Pakistan.

The present research study evaluate and identify the most suitable and high yielding genotypes of Lens culinaris for the salt marsh habitat of Swat in moist temperate sort of agro climatic environment of Pakistan. A total of fourteen genotypes were cultivated and analyzed through Randomized Complete Block Design (RCBD). These genotypes were AZRC-4, NL-2, NL4, NL-5, NL-6, NARC-11-1, NARC-11-2, NARC-11-3, NARC-11-4, 09503, 09505, 09506, P.Masoor-09 and Markaz-09. Different parameters i.e., germination rate, flowering, physiological maturity, plant height, biological grain yield, seed weight, pods formation and its height, pods per plants and protein content were focused specially throughout the study. Preliminary the Lentil genotypes have significant variability in all the major morpho-agronomic traits. The days to germination, 50% flowering and 100 seed weight ranged from 7 to 9, 110 to 116 days, and from 5.4 to 7.3 gm respectively. Biological yield and grain yield ranged from 5333 to 9777 kg ha-1 and 1933 to 3655 kg ha-1 respectively. Whereas, protein contents ranged from 23.21% to 28.45%. It was concluded that the genotype AZRC-4 is better varity in terms of grain yield plus in 100 seed weight and moreover, 09506 genotype was significant under salt marsh habitat in early maturing for the Swat Valley, Pakistan.

Formulation and Dissolution enhancement of Meloxicam tablets using Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and Povidone in combination.

Meloxicam is a poor water soluble drug mostly prescribed in various rheumatic diseases. The present research study was design to formulate and increase the solubility of meloxicam in the tablet dosage form. A 32 full factorial design was employed to optimize meloxicam formulations. Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVCL-PVA-PEG graft copolymer) and Povidone were taken as independent variables while cumulative drug release at 90 minutes was selected as dependent variable. All trial formulations complied with official standards. Multiple regression by Microsoft Excel on cumulative drug release of the selected formulations (F1, F2, F6- F9) showed the positive effect of PVCL-PVA-PEG graft copolymer (α = 0.05) and a negative effect of Povidone (α = 0.05). Formulation six (F6) (PVCL-PVA-PEG graft copolymer 3 mg and Povidone 22.5 mg / tablet) was considered as the optimal formulation based on its cumulative drug release. Dissolution kinetics by model dependent analysis predicted Weibull (R2=0.99) as the best fit model in describing meloxicam dissolution kinetics. The role of PVCL-PVA-PEG graft copolymer should be explored with other solubilizers in future studies.