DESIGN AND EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS USING SINTERING TECHNIQUE

Objective: Itopride Hydrochloride (ITO) is a prokinetic agent commonly used for the treatment of gastroesophageal reflux disease. It activates GI propulsive motility due to its dopamine D2 antagonizing activity and acetylcholinesterase inhibitory activity. The present work deals with application of sintering technique to matrix tablets of itopride hydrochloride to achieve sustained release using hydrophobic polymersMethods: Eudragit L-100 and carnauba wax were used in combination to achieve sustained release. A 32 factorial design was used to study the effect of sintering and various ratios of Eudragit and carnauba wax on percent drug release at 10 h, contact angle, and porosity. The tablets were also evaluated in terms of tensile strength, in-vitro dissolution and pharmacokinetic studies.Results: The results of a 32 full factorial design revealed that sintering caused decrease in drug release as compared to unsintered tablets. The concentration ratio of Eudragit L-100 and carnauba wax polymers also significantly affected the release profile. Carnauba wax maintained the integrity of the matrix, whereas Eudragit L-100 slowly eroded in the matrix as the drug was released. Thus, the area-to-volume ratio of the tablet remained constant over the duration of the drug release. The optimized formulation followed first order release kinetics with the diffusion-erosion mechanism. In vivo studies revealed higher Tmax of matrix tablet compared to a plain drug which is suggestive of slower absorption. However, the AUC0-10 h of the optimized formula and plain drug was found to be 1.561 h. µg/ml and 0.481 h. µg/ml respectively.Conclusion: Matrix tablets of Itopride hydrochloride can be formulated using the sintering technique to achieve sustained drug release along with increased bioavailability.Â

Do mutual funds have consistency in their performance?

Using a comprehensive data set of 714 Chinese mutual funds from 2004 to 2015, the study investigates these funds’ performance persistence by using the Capital Asset Pricing model, the Fama-French three-factor model and the Carhart Four-factor model. For persistence analysis, we categorize mutual funds into eight octiles based on their one year lagged performance and then observe their performance for the subsequent 12 months. We also apply Cross-Product Ratio technique to assess the performance persistence in these Chinese funds. The study finds no significant evidence of persis- tence in the performance of the mutual funds. Winner (loser) funds do not continue to be winner (loser) funds in the subsequent time period. These findings suggest that future performance of funds cannot be predicted based on their past performance.info:eu-repo/semantics/publishedVersio

Multiphase modelling of tumour growth and extracellular matrix interaction: mathematical tools and applications

Resorting to a multiphase modelling framework, tumours are described here as a mixture of tumour and host cells within a porous structure constituted by a remodelling extracellular matrix (ECM), which is wet by a physiological extracellular fluid. The model presented in this article focuses mainly on the description of mechanical interactions of the growing tumour with the host tissue, their influence on tumour growth, and the attachment/detachment mechanisms between cells and ECM. Starting from some recent experimental evidences, we propose to describe the interaction forces involving the extracellular matrix via some concepts coming from viscoplasticity. We then apply the model to the description of the growth of tumour cords and the formation of fibrosis

Recognizing recurrent neural networks (rRNN): Bayesian inference for recurrent neural networks

Recurrent neural networks (RNNs) are widely used in computational neuroscience and machine learning applications. In an RNN, each neuron computes its output as a nonlinear function of its integrated input. While the importance of RNNs, especially as models of brain processing, is undisputed, it is also widely acknowledged that the computations in standard RNN models may be an over-simplification of what real neuronal networks compute. Here, we suggest that the RNN approach may be made both neurobiologically more plausible and computationally more powerful by its fusion with Bayesian inference techniques for nonlinear dynamical systems. In this scheme, we use an RNN as a generative model of dynamic input caused by the environment, e.g. of speech or kinematics. Given this generative RNN model, we derive Bayesian update equations that can decode its output. Critically, these updates define a 'recognizing RNN' (rRNN), in which neurons compute and exchange prediction and prediction error messages. The rRNN has several desirable features that a conventional RNN does not have, for example, fast decoding of dynamic stimuli and robustness to initial conditions and noise. Furthermore, it implements a predictive coding scheme for dynamic inputs. We suggest that the Bayesian inversion of recurrent neural networks may be useful both as a model of brain function and as a machine learning tool. We illustrate the use of the rRNN by an application to the online decoding (i.e. recognition) of human kinematics

Comparison of an immortalized human corneal epithelial cell line with Vero cells in the isolation of Herpes simplex virus-1 for the laboratory diagnosis of Herpes simplex keratitis

BACKGROUND: Herpes simplex keratitis (HSK) is a sight threatening ocular infection often requiring a specific and prompt laboratory diagnosis. Isolation of Herpes simplex virus (HSV-1) in culture provides the most reliable and specific method and is considered as the "Gold Standard" in the laboratory diagnosis of HSK in spite of its low sensitivity. Using "cell lines of corneal origin" for virus isolation may be beneficial under such circumstances, since these cells have been shown to be excellent substrates for the growth of HSV-1 isolated from the cornea. We report a comparative study of a novel human corneal epithelial cell line (HCE) and the Vero cell line in the isolation of HSV-1 from corneal scrapings employing a shell vial assay. METHODS: Corneal scrapings were obtained from 17 patients with a clinical diagnosis of HSK. All the cases were confirmed by virological investigations (PCR and viral antigen detection positive, n = 15, PCR positive, n = 1, Viral antigen positive, n = 1). Scrapings obtained from 10 patients with infectious keratitis of non-viral origin were included as controls. All the scrapings were simultaneously inoculated into shell vials of HCE and Vero cells. Cultures were terminated at 24 h post-infection. Isolation of HSV-1 was confirmed using an indirect immunofluorescence/ immunoperoxidase assay. RESULTS: Virus could be isolated using both or either of the cell lines in 10/17 (58.82%) patients with HSK. HSV-1 was isolated from 10/ 17 (58.82%) and 4/17(23.52%) specimens in HCE and Vero cells, respectively (P = 0.036). None of the controls yielded HSV-1. While all the 10 (100%) strains were isolated in HCE, Vero yielded only 4/10 (40%) strains in the shell vial culture (P = 0.014). CONCLUSIONS: HCE showed a statistically significant difference in the virus isolation rate with respect to Vero cells. HCE may be an excellent alternative cell line for the isolation of HSV-1, especially from corneal scrapings, for the laboratory diagnosis of HSK

Design of transdermal patch of ketoprofen by full factorial design for treatment of rheumatoid arthritis

Oral therapy of NSAIDs for treatment of rheumatoid arthritis causes gastric irritation and ulceration. In the present study transdermal patch of ketoprofen was developed using hydroxyl propyl methyl cellulose E5 and Eudragit S100. Patches were prepared by solvent evaporation method. Optimization was carried out by 32 factorial design with polymer concentration (HPMC E5) and plasticizer concentration (propylene glycol) as independent variables. Patches were evaluated for folding endurance, surface pH, drug content, percent moisture content, water uptake and swelling studies. Ex vivo permeation studies of optimized patch was performed using Franz diffusion cell while bioadhesion force and tensile strength were measured by using texture analyzer. Hydrophilic nature, swelling ability and wettability of polymer and plasticizer were responsible for increase in flux and bioadhesion with increase in their concentrations in the factorial batches. Swelling index of all formulations was in the range of 17.3 ±1.2 to 65.29 ±4.78 up to 3h. Flux obtained from all batches was in the range of 3.37±0.23 to 5.43±0.13µg/h/cm2. Anti-inflammatory studies using carrageenan-induced rat paw edema showed greater paw swelling reduction in case of ketoprofen patch. Cumulative percent drug permeation of optimized patch through nylon 66, Wistar rat skin and cadaver skin was found to be 92.3% >86.28 %>63.42% in 8h, while flux order was 6.073> 5.442 > 2.219 µg/h/cm2 respectively. The study concludes that transdermal patch of ketoprofen will be more efficacious with absence of gastric irritation observed in oral formulations. Keywords: Ketoprofen, Bioadhesion, HPMC E5, Flux, Backing membran

Common extensor origin release in recalcitrant lateral epicondylitis - role justified?

The aim of our study was to analyse the efficacy of operative management in recalcitrant lateral epicondylitis of elbow. Forty patients included in this study were referred by general practitioners with a diagnosis of tennis elbow to the orthopaedic department at a district general hospital over a five year period. All had two or more steroid injections at the tender spot, without permanent relief of pain. All subsequently underwent simple fasciotomy of the extensor origin. Of forty patients thirty five had improvement in pain and function, two had persistent symptoms and three did not perceive any improvement. Twenty five had excellent, ten had well, two had fair and three had poor outcomes (recurrent problem; pain at rest and night). Two patients underwent revision surgery. Majority of the patients had improvement in pain and function following operative treatment. In this study, an extensor fasciotomy was demonstrated to be an effective treatment for refractory chronic lateral epicondylitis; however, further studies are warranted

Reinforcement learning or active inference?

This paper questions the need for reinforcement learning or control theory when optimising behaviour. We show that it is fairly simple to teach an agent complicated and adaptive behaviours using a free-energy formulation of perception. In this formulation, agents adjust their internal states and sampling of the environment to minimize their free-energy. Such agents learn causal structure in the environment and sample it in an adaptive and self-supervised fashion. This results in behavioural policies that reproduce those optimised by reinforcement learning and dynamic programming. Critically, we do not need to invoke the notion of reward, value or utility. We illustrate these points by solving a benchmark problem in dynamic programming; namely the mountain-car problem, using active perception or inference under the free-energy principle. The ensuing proof-of-concept may be important because the free-energy formulation furnishes a unified account of both action and perception and may speak to a reappraisal of the role of dopamine in the brain