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Abstract The purpose of the present study was to develop stable lyophilized formulation of peginterferon alfa-2b which is acquiescent to the short lyophilization process. The present study evaluates the effect of buffering components and cryoprotectant(s) on depegylation of the peginterferon alfa-2b in combination with lyophilization process. Finally, a short lyophilization process was identified which can produce a stable pharmaceutical form of peginterferon alfa-2b without any depegylation during long-term storage. Formulations were analyzed mainly for depegylation by HP-size exclusion chromatography and in-vitro antiviral activity. Residual moisture content in the lyophilized product was also used as a key indicating parameter to check its role with respect to depegylation upon storage under various temperature conditions. It was observed that the peginterferon alfa-2b when formulated in presence of cryoprotectant like sucrose requires longer lyophilization process of about 5 days, irrespective of the buffering components used, to reduce the level of residual moisture content and thereby to produce the stable formulation without depegylation. A stable formulation in presence of high concentration of lactose as a cryoprotectant was developed which can withstand stresses exerted to protein-polymer conjugate during lyophilization phases without any significant depegylation. A short lyophilization process of about 48 hours can be utilized for peginterferon alfa-2b when formulated in presence of lactose as a cryoprotectant through which a stable lyophilized formulation can be produced as against longer process required when sucrose is used a cryoprotectant, which is essential from commercial point of view as lyophilization is a costly process.

Over the past decades, comprehensive attempts have been made to improve physiological absorption by designing delivery systems, using suitable carriers, and altering the route of administration. Here, the vaginal route was targeted using capsular-shaped biodegradable in situ porous drug-eluting inserts (DEI) using clotrimazole as a model drug and PCL and PEO WSR 303 as rate-controlling polymers. Morphology, thermal properties, and degradation kinetics were assessed in comparison to non-porous DEI. The optimized DEI showed site-specific controlled drug release as per disease need, which may lead to enhanced bioavailability as well as patient compliance with reduced dose-related side effects. [ABSTRACT FROM AUTHOR]

This paper reports a detailed numerical investigation on the buckling aspects of laminated composite shell panels of three forms (cylindrical, spherical and hyperbolic paraboloid) with five support conditions exposed to linearly varying in-plane edge load employing eight nodded isoparametric finite element formulation. The impacts of different parameters including ply orientation, load factor, shell forms, aspect ratio, modulus ratio, curvature ratio, width-to-thickness ratio and angle of lamination on the buckling load of shell panels are examined. It is found that the various parameters addressed in this study have a remarkable impact on the buckling phenomena of laminated composite shell panels. Further, a comparison is made showing the effects of five types of compressive edge loads like uniform, triangular, parabolic, partial edge load and point load on the buckling phenomena of laminated shell panels with respect to five support conditions. [ABSTRACT FROM AUTHOR]

Background: Chronic cough, defined as a cough lasting 8 or more weeks, affects up to 10% of adults. Refractory chronic cough (RCC) is a cough that is uncontrolled despite comprehensive investigation and treatment of comorbid conditions while unexplained chronic cough (UCC) is a cough with no identifiable cause despite extensive evaluation of comorbid conditions. RCC and UCC are often poorly controlled. Understanding individuals' lived experience of the symptoms and impacts of these conditions may guide therapeutic strategies. Objectives: The primary objectives of this study were to assess respondents' perceptions of the key symptoms of RCC and UCC and the impacts of RCC and UCC and their symptoms on well-being, health-related quality of life, work productivity, and social relationships. Design: Qualitative study. Methods: This study enrolled 30 adults with physician-diagnosed RCC or UCC. Two trained qualitative researchers conducted individual, in-depth telephone interviews using a semi-structured interview guide. Interviews were audio-recorded, transcribed, coded, and systematically analyzed to identify content themes. Results: A total of 15 respondents with RCC and 15 with UCC were included in the study. Many respondents had RCC or UCC for a long duration (median 9 years, range: 0–24). Half of the respondents reported having a coughing episode at least once daily. Only 40% of respondents reported that medication had improved their symptoms. In over half of the respondents, RCC or UCC hindered communication, caused embarrassment, frustration, and worry, and lowered quality of life. Perceptions of meaningful treatment benefits in RCC or UCC varied widely across respondents. Conclusion: RCC and UCC remained poorly managed in many individuals and were associated with a wide range of symptoms and cough triggers that hindered daily activities and reduced emotional well-being. Understanding individuals' lived experiences may inform the development of RCC and UCC therapeutic strategies. Plain language summary: Patient-reported experiences with refractory or unexplained chronic cough: a qualitative analysis Chronic cough, particularly refractory and unexplained chronic cough, remain poorly managed in many individuals and are associated with a wide range of symptoms and cough triggers that hinder daily activities and reduce emotional well-being. Currently there are no US Food and Drug Administration-approved treatments for refractory or unexplained chronic cough. Understanding the experience and treatment preferences of individuals with these conditions may help inform the development of new therapies and clarify the potential impact of such therapies on the lives of individuals with chronic cough. Using in-depth interviews, the present study comprehensively evaluated individuals' experience with refractory or unexplained chronic cough and treatment priorities, a research area that has not been well-studied. This study detailed broad-ranging physical, behavioral, and emotional impacts of chronic cough, which hindered individuals' social well-being. [ABSTRACT FROM AUTHOR]

IMPORTANCE Photodynamic therapy (PDT) is used extensively to treat actinic keratoses(AKs). An analysis of the effectiveness of PDT compared with other treatments may help physicians decide what role it should play in their own clinical practices.OBJECTIVE To determine the effectiveness of PDT for the treatment of AKs relative to other methods.DATA SOURCES MEDLINE, EMBASE,Web of Knowledge, and Cochrane Central Register. No restrictions on years were placed, and all searches extended to the year of each data base inception. Our search was conducted on March 20, 2013, and included the search terms solar keratosis, actinic keratosis, photodynamic therapy, and photochemotherapy. No restrictions were used for the search string.STUDY SELECTION Only randomized PDT trials that used aminolevulinic acid hydrochloride ormethyl aminolevulinate hydrochloride as stabilizers with 10 or more participants were considered. Two of the authors undertook the search independently.DATA EXTRACTION AND SYNTHESIS Data were extracted independently by the 2 authors.We assessed data quality using the Jadad scoring system and used a random-effects model for pooled data analysis.MAIN OUTCOMES AND MEASURES Primary outcome measures specified a priori were lesion response, cosmetic results, and patient satisfaction after the intervention.RESULTS Our search identified 875 journal articles and meeting abstracts.We excluded 862 owing to lack of adherence to our inclusion criteria or lack of author response to our queries for further information.We assessed 13 studies for inclusion in our final synthesis, of which 4 were eligible for final meta-analysis. The only comparator for which meta-analysis was performed was cryotherapy. The meta-analysis consisted of 641 participants, with a total of 2174 AKs treated with cryotherapy and 2170 AKs treated with PDT. Compared with cryotherapy, the pooled relative risk for the meta-analysis for complete response (lesion clearance) was 1.14 (95%CI, 1.11-1.18) at 3 months after treatment. Visual inspection of a funnel plot revealed no publication bias, which was confirmed by the Begg test (P = .80).CONCLUSIONS AND RELEVANCE Photodynamic therapy has a 14%better chance of complete lesion clearance at 3 months after treatment than cryotherapy for thin AKs on the face and scalp.