In vitro evaluation of commercially available theophylline sustained release tablets in Pakistan

The dissolution behavior of five commercially available brands of sustained release theophylline tablets was studied in phosphate buffer solutions of pH 1.2, 4.5, 5.5, 6.0 and 7.5 at 37 °C using the USP dissolution apparatus II (paddle method). Drug concentration in the samples was determined spectrophotometrically at 272 nm. For predicting the release characteristics of theophylline from selected commercially available tablets the data obtained in the dissolution studies was fitted into various mathematic models defining kinetic parameters of drug release like zero-order rate equation, first-order rate equation, Hixen-crowell cube root law, Higuchi equation and Korsemeyer-Peppas model. Tablets were subjected to weight variation test, hardness, drug content and in vitro release studies. The present study revealed that drug release increases with the increase of pH of the dissolution medium and also varies from brand to brand. Among the five selected brands, B1 and B4 showed better pH dependency and drug release behaviour. It has been suggested that possible reasons for difference in dissolution or drug release behaviour are the difference in the manufacturing techniques and the quantity of hydrophobic excepients used by different manufacturers, which retard the penetration of dissolution medium and ultimately decreases availability of drug in the solution.Colegio de Farmacéuticos de la Provincia de Buenos Aire

In vitro evaluation of commercially available theophylline sustained release tablets in Pakistan

The dissolution behavior of five commercially available brands of sustained release theophylline tablets was studied in phosphate buffer solutions of pH 1.2, 4.5, 5.5, 6.0 and 7.5 at 37 °C using the USP dissolution apparatus II (paddle method). Drug concentration in the samples was determined spectrophotometrically at 272 nm. For predicting the release characteristics of theophylline from selected commercially available tablets the data obtained in the dissolution studies was fitted into various mathematic models defining kinetic parameters of drug release like zero-order rate equation, first-order rate equation, Hixen-crowell cube root law, Higuchi equation and Korsemeyer-Peppas model. Tablets were subjected to weight variation test, hardness, drug content and in vitro release studies. The present study revealed that drug release increases with the increase of pH of the dissolution medium and also varies from brand to brand. Among the five selected brands, B1 and B4 showed better pH dependency and drug release behaviour. It has been suggested that possible reasons for difference in dissolution or drug release behaviour are the difference in the manufacturing techniques and the quantity of hydrophobic excepients used by different manufacturers, which retard the penetration of dissolution medium and ultimately decreases availability of drug in the solution.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Does Race Affect Outcomes in Triple Negative Breast Cancer?

Background There is discordance among studies assessing the impact of race on outcome of patients with Triple Negative Breast Cancer (TNBC). We assessed survival outcomes for African American (AA) versus Caucasian (CA) women with TNBC treated at an urban cancer center in Memphis, TN with a predominant AA patient population. Methods Patients with Stage I-III TNBC were identified from our breast database. Event free survival (EFS) and Breast cancer specific survival (BCSS) were the primary outcome measures. Cox proportional hazards models were fitted for EFS and BCSS. Results Of the 124 patients, 71% were AA. No significant association between race and stage ( P = 0.21) or menopausal status ( P = 0.15) was observed. Median age at diagnosis was significantly lower for AA versus CA women (49.5 vs. 55 years, P = 0.024). 92% of the patients received standard neo/adjuvant chemotherapy, with no significant difference in duration and type of chemotherapy between the races. With a median follow up of 23 months, 28% of AA vs. 19% of CA women had an event ( P = 0.37). 3 year EFS and BCSS trended favorably towards CA race (77% vs. 64%, log rank P = 0.20 and 92% vs. 76%, P = 0.13 respectively) with a similar trend noted on multiple variable modeling (EFS: HR 0.62, P = 0.29; BCSS: HR 0.36, P = 0.18). AA women ≥50 years at diagnosis had a significantly worse BCSS than the CA women in that age group ( P = 0.012). Conclusion Older AA women with TNBC have a significantly worse breast cancer specific survival than their CA counterparts. Overall, there is a trend towards lower survival for AA women compared to Caucasians despite uniformity of tumor phenotype and treatment. The high early event rate, irrespective of race, underscores the need for effective therapies for women with TNBC

Intrinsic Inflation Persistence in a Developing Country

This study estimates degree of intrinsic inflation persistence in Pakistan using aggregate price index, group level price indices, and individual commodity prices. We find no evidence of a unit root in (MoM) inflation at any level, except for house rent. Using monthly data from 1959 to 2011 we find that the estimate of (overall) inflation persistence is 0.16, which is low but significant. During 2001-2011 (overall) inflation persistence is insignificant. Food inflation does not exhibit any persistence during the last decade. However, the degree of persistence is very high (0.80) and significant for core inflation (NFNE), which weakens slightly (to 0.69) when we account for commodities price shock of 2008. At micro level, the estimated degree of inflation persistence for various groups is found to be relatively higher, in almost 60 percent of the cases, compared to corresponding degree of persistence at aggregate level. This may be because in micro analysis we consider only those commodities for which the estimated degree of inflation persistence is significant

Intrinsic Inflation Persistence in a Developing Country

This study estimates degree of intrinsic inflation persistence in Pakistan using aggregate price index, group level price indices, and individual commodity prices. We find no evidence of a unit root in (MoM) inflation at any level, except for house rent. Using monthly data from 1959 to 2011 we find that the estimate of (overall) inflation persistence is 0.16, which is low but significant. During 2001-2011 (overall) inflation persistence is insignificant. Food inflation does not exhibit any persistence during the last decade. However, the degree of persistence is very high (0.80) and significant for core inflation (NFNE), which weakens slightly (to 0.69) when we account for commodities price shock of 2008. At micro level, the estimated degree of inflation persistence for various groups is found to be relatively higher, in almost 60 percent of the cases, compared to corresponding degree of persistence at aggregate level. This may be because in micro analysis we consider only those commodities for which the estimated degree of inflation persistence is significant

Analysis of trastuzumab and chemotherapy in advanced breast cancer after the failure of at least one earlier combination: An observational study

BACKGROUND: Combining trastuzumab and chemotherapy is standard in her2/neu overexpressing advanced breast cancer. It is not established however, whether trastuzumab treatment should continue after the failure of one earlier combination. In this trial, we report our experience with continued treatment beyond disease progression. METHODS: Fifty-four patients, median age 46 years, range 25–73 years, were included. We analysed for time to tumour progression (TTP) for first, second and beyond second line treatment, response rates and overall survival. RESULTS: Median time of observation was 24 months, range 7–51. Response rates for first line treatment were 7.4% complete remission (CR), 35.2% partial remissions (PR), 42.6% stable disease > 6 months (SD) and 14.8% of patients experienced disease progression despite treatment (PD). Corresponding numbers for second line were 3.7% CR, 22.2% PR, 42.6% SD and 31.5% PD; numbers for treatment beyond second line (60 therapies, 33 pts 3(rd )line, 18 pts 4(th )line, 6 pts 5(th )line, 2 pts 6(th )line and 1 patient 7(th )line) were 1.7% CR, 28.3% PR, 28.3% SD and 41.6% PD respectively. Median TTP was 6 months (m) in the first line setting, and also 6 m for second line and beyond second line. An asymptomatic drop of left ventricular ejection fraction below 50% was observed in one patient. No case of symptomatic congestive heart failure was observed. CONCLUSION: The data presented clearly strengthen evidence that patients do profit from continued trastuzumab treatment. The fact that TTP did not decrease significantly from first line to beyond second line treatment is especially noteworthy. Still, randomized trials are warranted

Alichur Dome, South Pamir, Western India-Asia Collisional Zone: Detailing the Neogene Shakhdara-Alichur Syn-collisional Gneiss-Dome Complex and Connection to Lithospheric Processes

Neogene, syn‐collisional extensional exhumation of Asian lower–middle crust produced the Shakhdara–Alichur gneiss‐dome complex in the South Pamir. The <1 km‐thick, mylonitic–brittle, top‐NNE, normal‐sense Alichur shear zone (ASZ) bounds the 125 × 25 km Alichur dome to the north. The Shakhdara dome is bounded by the <4 km‐thick, mylonitic–brittle, top‐SSE South Pamir normal‐sense shear zone (SPSZ) to the south, and the dextral Gunt wrench zone to its north. The Alichur dome comprises Cretaceous granitoids/gneisses cut by early Miocene leucogranites; its hanging wall contains non/weakly metamorphosed rocks. The 22–17 Ma Alichur‐dome‐injection‐complex leucogranites transition from foliation‐parallel, centimeter‐ to meter‐thick sheets within the ASZ into discordant intrusions that may comprise half the volume of the dome core. Secondary fluid inclusions in mylonites and mylonitization‐temperature constraints suggest Alichur‐dome exhumation from 10–15 km depth. Thermochronologic dates bracket footwall cooling between ~410–130 °C from ~16–4 Ma; tectonic cooling/exhumation rates (~42 °C/Myr, ~1.1 km/Myr) contrast with erosion‐dominated rates in the hanging wall (~2 °C/Myr, <0.1 km/Myr). Dome‐scale boudinage, oblique divergence of the ASZ and SPSZ hanging walls, and dextral wrenching reflect minor approximately E–W material flow out of the orogen. We attribute broadly southward younging extensional exhumation across the central South Pamir between ~20–4 Ma to: (i) Mostly northward, foreland‐directed flow of hot crust into a cold foreland during the growth of the Pamir orocline; and (ii) Contrasting effects of basal shear related to underthrusting Indian lithosphere, enhancing extension in the underthrust South Pamir and inhibiting extension in the non‐underthrust Central Pamir

Fabrication and Biological Assessment of Antidiabetic α-Mangostin Loaded Nanosponges: In Vitro, In Vivo, and In Silico Studies

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-29, pub-electronic 2021-11-01Publication status: PublishedFunder: King Saud University; Grant(s): RSP-2021/406Type 2 diabetes mellitus has been a major health issue with increasing morbidity and mortality due to macrovascular and microvascular complications. The urgent need for improved methods to control hyperglycemic complications reiterates the development of innovative preventive and therapeutic treatment strategies. In this perspective, xanthone compounds in the pericarp of the mangosteen fruit, especially α-mangostin (MGN), have been recognized to restore damaged pancreatic β-cells for optimal insulin release. Therefore, taking advantage of the robust use of nanotechnology for targeted drug delivery, we herein report the preparation of MGN loaded nanosponges for anti-diabetic therapeutic applications. The nanosponges were prepared by quasi-emulsion solvent evaporation method. Physico-chemical characterization of formulated nanosponges with satisfactory outcomes was performed with Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Zeta potential, hydrodynamic diameter, entrapment efficiency, drug release properties, and stability studies at stress conditions were also tested. Molecular docking analysis revealed significant interactions of α-glucosidase and MGN in a protein-ligand complex. The maximum inhibition by nanosponges against α-glucosidase was observed to be 0.9352 ± 0.0856 µM, 3.11-fold higher than acarbose. In vivo studies were conducted on diabetic rats and plasma glucose levels were estimated by HPLC. Collectively, our findings suggest that MGN-loaded nanosponges may be beneficial in the treatment of diabetes since they prolong the antidiabetic response in plasma and improve patient compliance by slowly releasing MGN and requiring less frequent doses, respectively