Matrix-type System Research Articles

Transdermal Delivery of Azilsartan: Formulation Strategies and Performance Evaluation

Aims: Matrix-type systems were developed in the present study by using various polymers including sodium carboxymethyl cellulose and eudragits with various concentrations. Materials and Methods: In the present work, an attempt has been made to develop a matrix-type transdermal therapeutic system comprising of Azilsartan with different concentrations of sodium carboxyl methyl cellulose and Eudragit using solvent evaporation technique. The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy. Results and Discussion: The results obtained showed no physical-chemical incompatibility between the drug and the polymers. The in vitro drug diffusion studies from the formulation were found to be a sustained release effect. All the evaluation parameters obtained from the best formulation were found to be satisfactory. Conclusion: The data obtained from the in vitro release studies were fitted to various kinetic models; it was found that drug release follows the Peppas model release by diffusion technique from the polymer.

Formulation and evaluation of inclusion complexed repaglinide with β-cyclodextrin transdermal patches

Chronic diseases such as diabetes mellitus have high prevalence all over the world. The purpose of the study is to prepare a transdermal patch that can be used to treat diabetes, reducing pill burden and increasing patient compliance. Based on positive results of a feasibility study, including doctor’s opinion and prescription survey, repaglinide was selected as the active ingredients for developing a transdermal patch. The complexation of repaglinide and β cyclodextrin was done by grinding method. The present study was designed to develop Matrix type systems of transdermal patch containing repaglinide- β cyclodextrin complexes, using different polymeric combinations such as Hydroxy Propyl Methyl cellulose (HPMC), Ethyl Cellulose (EC), and Eudragit L100 with Poly vinyl pyrolidone (PVP) by solvent evaporation technique. The patches were subjected to physicochemical parameters, in-vitro drug release and in-vitro skin permeation studies. Good results were obtained in all the evaluated parameters. The developed transdermal delivery system containing complex of repaglinide and β cyclodextrin can further be studied for launching it in market.

On stochastic Kaczmarz type methods for solving large scale systems of ill-posed equations

In this article we investigate a family of stochastic gradient type methods for solving systems of linear ill-posed equations. The method under consideration is a stochastic version of the projective Landweber–Kaczmarz method in Leitão and Svaiter (2016 Inverse Problems 32 025004) (see also Leitão and Svaiter (2018 Numer. Funct. Anal. Optim. 39 1153–80)). In the case of exact data, mean square convergence to zero of the iteration error is proven. In the noisy data case, we couple our method with an a priori stopping rule and characterize it as a regularization method for solving systems of linear ill-posed operator equations. Numerical tests are presented for two linear ill-posed problems: (i) a Hilbert matrix type system with over 108 equations; (ii) a big data linear regression problem with real data. The obtained results indicate superior performance of the proposed method when compared with other well-established random iterations. Our preliminary investigation indicates that the proposed iteration is a promising alternative for computing stable approximate solutions of large scale systems of linear ill-posed equations.

A Comparative Study of Levocetirizine Loaded Vesicular and Matrix Type System for Topical Application: Appraisal of Therapeutic Potential against Atopic Dermatitis

Topical drug delivery offers improved therapeutic effect and reduced systemic adverse effects of the administered compounds. The present work was aimed at developing and comparing levocetirizine loaded polymeric nanoparticles and niosomal formulation(s), respectively, against dinitrochlorobenzene-induced atopic dermatitis animal model. The niosome and chitosan nanoparticle were developed and evaluated for particle size distribution, drug loading, and entrapment efficiency. The formulations were optimized through Box-Behnken design. The optimized formulations were dispersed in carbopol gel and evaluated for ex vivo permeation, retention, and in vivo studies. The optimized niosomes and chitosan nanoparticle exhibited a particle size range of 384.4 ± 64.3 nm and 382.7 ± 59.2 nm, drug loading of 18.99 ± 0.02% and 12.2 ± 1.6%, and entrapment efficiency of 46.63 ± 2.12% and 29.6 ± 1.6%, respectively. The permeation and retention studies displayed less permeation and significantly (p < 0.01) high retention percentage of LCZD by OPT-N gel when compared with OPT-CN gel. In in vivo studies revealed that OPT-N significantly (p < 0.05) reduces erythema score (from 3 to 1) and scratching frequency (70–25 scratches/20 min). OPT-N gel shows high entrapment efficiency and skin retention capacity of the drug along with better topical applicability and higher therapeutic efficacy. The OPT-N also manifested the maximum peripheral action of LCZD against AD as compared with optimized chitosan gel and plain LCZD gel.

Economic impact of port sectors on South African economy: An input–output analysis

The port sectors in a country play an important role in its economy. This paper presents an input–output analysis on how the port sectors impact a concerned economy using the South African case. Moreover, this paper reports how a rectangular Supply and Use Table system of national accounts can be converted to a traditional square symmetric matrix type system. A range of models, such as demand-driven, supply-driven and price models, were derived for the estimation. From these models, the production effect together with the forward and backward linkage effects, price change effects and employment effects were estimated to determine the impact of port sectors. The overall forward linkage effect of the port sector was 0.97 and the backward one was 0.48, indicating that the port sector does not appear to use other sectors much in producing its activities whereas the port sector is used relatively more by other industries owing to its relatively high forward linkage effect. The overall impact effect of the port sector per unit shortage on all other products was found to be 1.1705. Therefore, one unit shortage in the port sector would have incurred a 17% loss to the entire economy in 2002. Leontief׳s price model was used for the scenario that what would occur if the price of port sector׳s cost was increased by various ranges from 5%, 10% and 30% to 50% and 100%.

Recent Advances in Chitosan Films for Controlled Release of Drugs

Chitosan is a versatile carrier for biologically active agent from a small molecule such as an antibiotic to macromolecules such as proteins and nucleic acids. In addition, drug delivery devices based on chitosan can be available in a variety of morphologies including films, fibers, nanoparticles and microspheres. Otherwise the inherent advantages of this polymer such as biocompatibility, tissue adhesions and hydrophilic nature, chitosan can be modified to accomplish a specific purpose, for example improves release kinetics. In this review, recent patents of chitosan-based film systems for drug delivery are presented and discussed. This review include matrix type systems, membrane coated systems and film forming solution. For each one of these systems, several examples of manufacture processes, bioactive agents to be delivered and specifics applications are considered. This work highlights the use of chitosan in the film technology for drug delivery, presenting examples of chitosan used in an unmodified state and examples of modifications of the polymer backbone.

Polymer Percolation Threshold in Multi-Component HPMC Matrices Tablets.

The percolation theory studies the critical points or percolation thresholds of the system, where one component of the system undergoes a geometrical phase transition, starting to connect the whole system.The application of this theory to study the release rate of hydrophilic matrices allows to explain the changes in release kinetics of swellable matrix type system and results in a clear improvement of the design of controlled release dosage forms. In this study, the percolation theory has been applied to multi-component hydroxypropylmethylcellulose (HPMC) hydrophilic matrices. Matrix tablets have been prepared using phenobarbital as drug, magnesium stearate as a lubricant employing different amount of lactose and HPMC K4M as a filler and matrix forming material, respectively. Ethylcelullose (EC) as a polymeric excipient was also examined. Dissolution studies were carried out using the paddle method.In order to estimate the percolation threshold, the behaviour of the kinetic parameters with respect to thevolumetric fraction of HPMC at time zero, was studied. In both HPMC/lactose and HPMC/EC/lactose matrices, from the point of view of the percolation theory, the optimum concentration for HPMC, to obtain a hydrophilic matrix system for the controlled release of phenobarbital is higher than 18.1% (v/v) HPMC. Above 18.1% (v/v) HPMC, an infinite cluster of HPMC would be formed maintaining integrity of the system and controlling the drug release from the matrices. According to results, EC had no significant influence on the HPMC percolation threshold. This may be related to broad functionality of the swelling hydrophilic matrices.

Validated GC–MS analysis for the determination of residual fentanyl in applied Durogesic ® reservoir and Durogesic ® D-Trans ® matrix transdermal fentanyl patches

The method development and validation characteristics are described of a simple gas chromatographic–mass spectrometric (GC–MS) analytical procedure to determine residual fentanyl in used Durogesic ® reservoir patches and Durogesic ® D-Trans ® matrix technology based systems to estimate the actual rate of transdermal fentanyl delivered in individual patients. The sample preparation protocol constituting a saline based extraction of sets of new patches of each nominal dose available, resulted in fentanyl extraction recoveries to increase steadily as a function of increasing extraction time. For the reservoir type transdermal therapeutic system (TTS), fentanyl extraction efficiencies at equilibrium (16 h) ranged from approximately 60% (100-μg/h TTS) to 95% (25-μg/h TTS), whereas for the matrix type system considerable lower recoveries were demonstrated for the highest nominal dose rates (35%–52%), while reaching 90% for the 25-μg/h system. For the latter type of fentanyl TTS, an optimized methanol based extraction protocol yielded virtually quantitative fentanyl recoveries for each matrix patch nominal dose level at substantially shorter extraction periods (15 min). The GC–MS analytical method using selected ion monitoring (SIM) and deuterated fentanyl as internal standard was shown to be adequately selective with regard to the presence of other compounds in the Durogesic ® patches. It was further demonstrated that the developed analytical protocols provided highly reproducible and accurate estimates of the initial fentanyl content of each patch type at all available nominal doses, with coefficients of variation and relative errors generally below 10%. These advantageous assay validation characteristics can be further transposed to the application of residual fentanyl level estimates in used patches, provided that with each batch of samples also a set of new TTSs with equal dose is assayed to perfectly mimic extraction phenomena. Finally, the presented GC–MS analytical protocol was successfully applied for the determination of residual fentanyl in a subset of 57 reservoir type patches obtained from four palliative patients.

Microstructure and release characteristics of the minipellet, a collagen-based drug delivery system for controlled release of protein drugs

We have developed the minipellet, a matrix-type system for the sustained delivery of protein drugs using collagen as a biodegradable drug carrier. In this study, we analyzed the microstructure and release profile of the minipellet containing human serum albumin (HSA) as a model drug.The findings suggest that the minipellet has a structure in which collagen fibers are strongly oriented in the direction of extrusion from the nozzle in the molding process of the minipellet, and that HSA exists as fine particulate clusters which are homogeneously distributed among the collagen fibers in the minipellet. During release, the HSA clusters dissolve and HSA is retained within the collagen matrix as a solution.The results of release experiments indicate that HSA release from the minipellet is mainly controlled by diffusion in the collagen matrix, and that sustained release is achieved by the dense structure of the collagen matrix which is formed in the manufacture process. In addition, more detailed study suggests that the minipellet has unique directional release behavior caused by its microstructure.

Controlled Drug Release from a Compressed Heterogeneous Polymeric Matrix: Kinetics of Release

A physical model of a new matrix-type system is presented where constant drug release can be maintained irrespective of the extent of the tortuosity and receding drug boundary. Theophylline base was dispersed as discrete crystals and fine particles in a matrix formed by the cross-linking of polymeric mixtures consisting of PEG, acrylic resins and ethyl cellulose. DSC analysis was performed to identify any solid state inactivation of the drug. Concave tablets at specified pressures were prepared in order to achieve a wide range of release rates and patterns of release. It was found that the patterns of release could be controlled by the formulation components and the manufacturing procedures. Drug release rates were determined spectrophotometrically under sink conditions and the flux of drug release, dQ/dt, from these matrix-type delivery systems was almost constant over 15 hours, during which time about 85% of the active drug was released. The release rate was devoid of any hydrodynamic boundary effect an...