Formulation and evaluation of a sublingual tablet containing terbutaline sulphate: optimisation and in vivo studies

La finalidad de este trabajo de investigación es la formulación de un comprimido sublingual de sulfatode terbutalina de acción rápida y mejorar la biodisponibilidad y el cumplimiento de las pautas por partedel paciente. Para la preparación de los gránulos se utilizó una técnica de granulación húmeda. Seprepararon formulaciones basadas en el diseño factorial con variables de formulación 32: la cantidad decelulosa microcristalina (MCC) (X1) y la crospovidona como componente bioadhesivo (X2). Comovariables de respuesta se evaluaron la resistencia al aplastamiento, la friabilidad y el tiempo de desintegración(DT). Los principales efectos y términos de interacción se evaluaron cuantitativamente medianteun modelo cuadrático. Los resultados revelaron que la cantidad de MCC y crospovidona afectabansignificativamente a las variables de respuesta. La formulación optimizada de comprimidos contiene 31,5mg de MCC y 4,5 mg de crospovidona, se desintegra en un período corto con un índice DT de 30,2+ 5,5 seg. y tiene una resistencia al aplastamiento suficiente y una friabilidad aceptable. Las concentracionesplasmáticas de terbutalina se obtuvieron a los 5 minutos. Los resultados indican que lacrospovidona, un componente bioadhesivo, impide tragar la terbutalina, sin afectar a su liberación yabsorción. En conclusión, la formulación del comprimido sublingual se puede extrapolar a otros fármacosen los que se desee una absorción rápida.The objective of this research was to formulate a sublingual tablet formulation of terbutaline for rapidaction, and to improve both bioavailability and patient compliance to therapy. A wet granulation techniquewas adapted to prepare the granules. Granule formulations were prepared using an adapted wet granulationtechnique based on a 32 full factorial design. The formulation variables were expressed as follows;quantity of microcrystalline cellulose (MCC), (X1), and bioadhesive component crospovidone, (X2),while crushing strength, friability and disintegration time (DT) were determined as response variables.The main effects and interaction terms were quantitatively evaluated using a quadratic model. The resultsobtained showed that the quantity of MCC and crospovidone significantly affect response variables. Anoptimised tablet formulation, containing 31.5 mg of MCC and 4.5 mg of crospovidone, provides a shortDT of 30.2 + 5.5 sec with sufficient crushing strength and acceptable friability, while DT for serumconcentrations of terbutaline were obtained within 5 min. The results indicate that the inclusion ofcrospovidone, a bioadhesive component, in sublingual tablet formulations, makes the swallowing of tablets unnecessary, because the release and absorption of the terbutaline in such formulations isacceptably effective. In conclusion, the developed sublingual tablet formulations is of interest, becauseit can be extrapolated to other drugs, where rapid absorption is desirable

Formulation and Evaluation of Bioadhesive Cyproheptadine Tablets

Purpose: To evaluate the effect of formulation variables on the bioadhesion and release properties of bioadhesive cyproheptadine hydrochloride tablets.Methods: Screening of polymers - hydroxypropyl methylcellulose, (HPMC), sodium carboxy methyl cellulose (CMC), and Carbopol 974p and 934p - in solution form were carried out by shear stress and detachment force measurement,based on Taguchi model, in order to determine their bioadhesion properties. Central composite design (CCD) was applied to optimize the combined effects of the polymers on release rate constant (K), diffusion coefficient (n), regression coefficient (R2) and detachment force of a sustained release tablet formulation of cyproheptadine hydrochloride containing also a prompt dose of the drug.Results: The shear stress of 3 % solution of HPMC was greater than that of an equivalent concentration of Carbopol 934P. The values of K, n, R2 and detachment force for the optimized formulation (F0) were 0.269, 0.696, 0.964 and 0.066 Newton (N), respectively, and showed good correlation with the predicted values, thus confirming the practicability and validity of the model.Conclusion: Gastric retention time can be increased for cyproheptadine hydrochloride by formulating it as a bioadhesive tablet that enhances the retention of the dosage form in the stomach and hence gastric absorption of the drug.Keywords: Cyproheptadine hydrochloride, Bioadhesive core tablet, Detachment force, Taguchi design, Central composite desig

The Effect of Rural-to-Urban Migration on Obesity and Diabetes in India: A Cross-Sectional Study

Shah Ebrahim and colleagues examine the distribution of obesity, diabetes, and other cardiovascular risk factors among urban migrant factory workers in India, together with their rural siblings. The investigators identify patterns of change of cardiovascular risk factors associated with urban migration

Long-term outcome and prognosis of dissociative disorder with onset in childhood or adolescence

<p>Abstract</p> <p>Background</p> <p>In the majority of cases short-term treatment outcome of juvenile dissociative disorder is rather favourable. In contrast, the long-term course seems to be less positive, but meaningful results are still fragmentary. The aim of this follow-up study is to bridge this gap to some extent describing the long-term outcome of juvenile dissociative disorder in a clinical sample. To our knowledge there is no comparable other long-term follow-up study which is based on a case definition according to actual classification systems using standardized interviews for individual assessment of the patients at the time of follow-up.</p> <p>Methods</p> <p>The total study group was made up of all patients treated for dissociative disorder at our department for child and adolescent psychiatry between 1983 and 1992 (<it>N </it>= 62). Two of these former patients committed suicide during the follow-up period (3%). We got information on the clinical course of 27 former patients (44%). 17 out of these 27 former patients were female (63%). The mean age of onset of dissociative disorder was11.7 years and the mean follow-up time was 12.4 years. Most of the patients were reassessed personally (n = 23) at a mean age of 24.8 years using structured interviews covering dissociative disorders, other Axis I disorders and personality disorders (Heidelberg Dissociation Inventory HDI; Expert System for Diagnosing Mental Disorders, DIA-X; Structured Clinical Interview for DSM-IV, SCID-II). Social adjustment was assessed by a semi-structured interview and by patient self report (Social Adjustment Scale – Self Report, SAS-SR). Psychosocial outcome variables were additionally assessed in 36 healthy controls (67% female, mean age = 22.9 years).</p> <p>Results</p> <p>At the time of follow-up investigation 82.6% of the patients met the criteria for some form of psychiatric disorder, while 26.1% were still suffering from dissociative disorder. A total of 56.5% presented with an Axis I disorder (especially anxiety, dissociative and somatoform disorders). Personality disorders were seen in 47.8% (especially borderline, obsessive-compulsive and negativistic personality disorders). More dissociative symptoms and inpatient treatment in childhood or adolescence were significantly related to a lower level of psychosocial adjustment in adulthood.</p> <p>Conclusion</p> <p>Treatment strategies have to consider that in a significant portion of young patients initial recovery may not be stable over time. Limitations of the study refer to the small sample size and the low rate of former patients taking part in the follow-up investigation.</p

Multi-center feasibility study evaluating recruitment, variability in risk factors and biomarkers for a diet and cancer cohort in India

<p>Abstract</p> <p>Background</p> <p>India's population exhibits diverse dietary habits and chronic disease patterns. Nutritional epidemiologic studies in India are primarily of cross-sectional or case-control design and subject to biases, including differential recall of past diet. The aim of this feasibility study was to evaluate whether a diet-focused cohort study of cancer could be established in India, providing insight into potentially unique diet and lifestyle exposures.</p> <p>Methods</p> <p>Field staff contacted 7,064 households within three regions of India (New Delhi, Mumbai, and Trivandrum) and found 4,671 eligible adults aged 35-69 years. Participants completed interviewer-administered questionnaires (demographic, diet history, physical activity, medical/reproductive history, tobacco/alcohol use, and occupational history), and staff collected biological samples (blood, urine, and toenail clippings), anthropometric measurements (weight, standing and sitting height; waist, hip, and thigh circumference; triceps, sub-scapula and supra-patella skin fold), and blood pressure measurements.</p> <p>Results</p> <p>Eighty-eight percent of eligible subjects completed all questionnaires and 67% provided biological samples. Unique protein sources by region were fish in Trivandrum, dairy in New Delhi, and pulses (legumes) in Mumbai. Consumption of meat, alcohol, fast food, and soft drinks was scarce in all three regions. A large percentage of the participants were centrally obese and had elevated blood glucose levels. New Delhi participants were also the least physically active and had elevated lipids levels, suggesting a high prevalence of metabolic syndrome.</p> <p>Conclusions</p> <p>A high percentage of participants complied with study procedures including biological sample collection. Epidemiologic expertise and sufficient infrastructure exists at these three sites in India to successfully carry out a modest sized population-based study; however, we identified some potential problems in conducting a cohort study, such as limited number of facilities to handle biological samples.</p

Oblivious Pseudorandom Functions from Isogenies

An oblivious PRF, or OPRF, is a protocol between a client and a server, where the server has a key $k$ for a secure pseudorandom function $F$, and the client has an input $x$ for the function. At the end of the protocol the client learns $F(k,x)$, and nothing else, and the server learns nothing. An OPRF is verifiable if the client is convinced that the server has evaluated the PRF correctly with respect to a prior commitment to $k$. OPRFs and verifiable OPRFs have numerous applications, such as private-set-intersection protocols, password-based key-exchange protocols, and defense against denial-of-service attacks. Existing OPRF constructions use RSA-, Diffie-Hellman-, and lattice-type assumptions. The first two are not post-quantum secure. In this paper we construct OPRFs and verifiable OPRFs from isogenies. Our main construction uses isogenies of supersingular elliptic curves over $\mathbb{F}_{p^{2}}$ and tries to adapt the Diffie-Hellman OPRF to that setting. However, a recent attack on supersingular-isogeny systems due to Galbraith et al. [ASIACRYPT 2016] makes this approach difficult to secure. To overcome this attack, and to validate the server\u27s response, we develop two new zero-knowledge protocols that convince each party that its peer has sent valid messages. With these protocols in place, we obtain an OPRF in the SIDH setting and prove its security in the UC framework. Our second construction is an adaptation of the Naor-Reingold PRF to commutative group actions. Combining it with recent constructions of oblivious transfer from isogenies, we obtain an OPRF in the CSIDH setting

Silent assassin: Coronary artery disease in a type II diabetic

Case Presentation A 53 year old white male with a past medical history significant for type II diabetes mellitus and orthotopic liver transplant (December 2006) secondary to hepatitis B cirrhosis presents as a direct admission to Thomas Jefferson University Hospital in September 2007 for an orthopedic preoperative risk evaluation. Patient has had a dull, worsening, non-radiating back pain of six months duration, beginning after his liver transplant for which he has been to several outpatient orthopedic physicians. Upon admission, the patient appeared well, but admitted to a consistent 8/10 back pain that he had been managing at home with narcotic medications. Of note, outpatient magnetic resonance imaging (MRI) showed diskitis at L4/L5. Spinal biopsy and cultures were performed to rule out cord compression, spinal injury and infection due to his previous surgery and were all negative. On review of systems, he denied any lower extremity tenderness, numbness, paresthesias or loss of bowel or bladder function. He has lost over 70 pounds since his liver transplant. The remainder of the patient’s past medical history was negative except for a history of cataracts due to his diabetes mellitus. He reports a strong family history of hypertension, coronary artery disease and both type I and type II diabetes mellitus

Formulation and Evaluation of Bioadhesive Cyproheptadine Tablets

Purpose: To evaluate the effect of formulation variables on the bioadhesion and release properties of bioadhesive cyproheptadine hydrochloride tablets. Methods: Screening of polymers - hydroxypropyl methylcellulose, (HPMC), sodium carboxy methyl cellulose (CMC), and Carbopol 974p and 934p - in solution form were carried out by shear stress and detachment force measurement,based on Taguchi model, in order to determine their bioadhesion properties. Central composite design (CCD) was applied to optimize the combined effects of the polymers on release rate constant (K), diffusion coefficient (n), regression coefficient (R2) and detachment force of a sustained release tablet formulation of cyproheptadine hydrochloride containing also a prompt dose of the drug. Results: The shear stress of 3 % solution of HPMC was greater than that of an equivalent concentration of Carbopol 934P. The values of K, n, R2 and detachment force for the optimized formulation (F0) were 0.269, 0.696, 0.964 and 0.066 Newton (N), respectively, and showed good correlation with the predicted values, thus confirming the practicability and validity of the model. Conclusion: Gastric retention time can be increased for cyproheptadine hydrochloride by formulating it as a bioadhesive tablet that enhances the retention of the dosage form in the stomach and hence gastric absorption of the drug