Release kinetics of hydroxypropyl methylcellulose governing drug release and hydrodynamic changes of matrix tablet

Background: Hydrophilic hydroxypropyl methylcellulose (HPMC) matrix tablets are the standard role model of the oral controlled-release formulation. Nevertheless, the HPMC kinetics for the mechanistic understanding of drug release and hydrodynamic behaviors are rarely investigated. This study aims to investigate the release behaviors of both HPMC and paracetamol (model drug) from the hydrophilic matrix tablet. Methods: Two different viscosity grades of HPMC were used (Low viscosity: 6 cps, High viscosity: 4,000 cps). Three different ratios of drug/HPMC (H:38.08%, M:22.85%, and L:15.23% (w/w) of HPMC amounts in total weight) matrix tablets were prepared by wet granulation technique. The release profiles of the drug and HPMC in a matrix tablet were quantitatively analyzed by HPLC and 1H-nuclear magnetic resonance (NMR) spectroscopy. The hydrodynamic changes of HPMC were determined by the gravimetric behaviors such as swelling and erosion rates, gel layer thickness, front movement data,and distributive near-infrared (NIR) chemical imaging of HPMC in a matrix tablet during the dissolution process. Results: High viscosity HPMC tablets showed slower release of HPMC than the release rate of drug, suggesting that drug release preceded polymer release.Different hydration phenomenon was qualitatively identified and corresponded to the release profiles. The release behaviors of HPMC and drug in the tablet could be distinguished with the significant difference with fitted dissolution kinetics model (Low viscosity HPMC 6cps; Korsmeyer-Peppas model, High viscosity HPMC 4000cps; Hopfenberg model, Paracetamol; Weibull model) according to the weight of ingredients and types of HPMC. Conclusion: The determination of HPMC polymer release correlating with drug release, hydrodynamic behavior, and NIR chemical imaging of HPMC can provide new insights into the drug release-modulating mechanism in the hydrophilic matrix system.

Gel Strength of Hydrophilic Matrix Tablets in Terms of In Vitro Robustness

Purpose The purpose of this study was to correlate the gel strength of swollen matrix tablets with their in vitro robustness against agitation intensity and applied mechanical forces. Five commercial products, i.e. Glucophage®, Alfuzosin®, Tromphyllin®, Preductal® MR and Quetiapin® formulated as water-soluble/erodible matrix tablets were investigated. Methods Effect of agitation speed (50–150 rpm) on drug release, hydration/erosion and gel strength was investigated using USP paddle apparatus II. The gel strength of matrix tablets during dissolution at different conditions was characterized by a texture analyzer. Results Commercial tablets formulated with HPMC of higher viscosity, such as K15M or K100M, demonstrated the gel strength in swollen state >0.02 MPa. In this case, the release mechanism was predominantly diffusional and, therefore, not affected by stirring speed and mechanical stress. In contrast, the Quetiapin® matrix tablet, formulated with HPMC K 4 M in amount of approx. 25%, demonstrated the gel strength dropped below 0.02 MPa after 6 h of release. In this case, the drug was predominantly released via erosional mechanism and very susceptible to stirring speed. Conclusion Sufficient gel strength of swollen tablets is an important prerequisite for unchanged in vitro performance in consideration of mechanical stress.

DISSOLUTION KINETIC OF MELOXICAM FROM HYDROPHILIC MATRIX-TYPE FILMS FOR TRANSDERMAL THERAPY

Taking into consideration the fact the transdermal administration of the active pharmaceutical ingredients can represent a therapeutic approach that increases the patient’s compliance, this study aims to evaluate the release of meloxicam (MX), a potent non-steroidal anti-inflammatory drug, incorporated in hydrophilic polymer-based matrices for transdermal therapeutic systems was studied. Three different formulations were realized by solvent casting method containing two types of hydroxypropyl methylcellulose (HPMCE5 with low viscosity and HPMC15000 with high viscosity) whose concentration was also varied. The drug release test was performed by Franz diffusion cell and the dissolution curves were analysed from a kinetical point of view by model dependent and model independent methods. Linearization by simple regression allowed the flux calculations of values that varied between 0.183 and 32.270 g/(cm2h). Based on the results obtained with the mathematical analysis, we can conclude that the MX release is influenced by the pH of the dissolution media and by the type and concentration of the matrix forming agent. Discrimination of model dependent mathematical models was done by the Akaike index with values between 49 and -62. The kinetic analysis of the MX releasing curves from the proposed formulations showed that Korsmeyer-Peppas was more suitable for the release characterisation of the active pharmaceutical ingredient from the transdermal therapeutic systems analysed.

Enhancement of Solubility and Dissolution Rate of Curcumin Using Porous Starch by Solid Dispersion Technique

The poor dissolution characteristics of biopharmaceutical class II drugs are a major concern for scientists in thepharmaceutical industry. Solid dispersion is introduced as a novel method for enhancement of solubility. Class IIdrugs are low solubility and high permeability according to the biopharmaceutical classification system and arepromising candidates for improving solubility and bioavailability through solid dispersion. The purpose of the present attempt is to prepare a solid dispersion of curcumin and porous starch in order to increase the solubility and dissolution of drugs that are poorlysoluble. Solid dispersions (SDs) of BCS-II drugs were prepared by ball milling in ratio of drug: polymer i.e. curcumin: porous starch (1:0.5, 1:1, 1:2 and 1:3). Further, SDs were investigated by solubility, FTIR, XRD, DSC, micromeritics, and in-vitro dissolution. . Conclusively, porous starch offers a hydrophilic matrix to deliver poorwater soluble drugs and Solid dispersion system have demonstrated an improved performance. Solid dispersionsystem have demonstrated an improved performance

Effect of Different Types of Polymers as Well as Different Preparation Techniques on the In-Vitro Release of Dyphylline Controlled Release Matrix Tablets

Dyphylline, xanthine derivatives, is used to manage asthma, cardiac dyspnea, chronic bronchitis, and emphysema. This work aimed to develop controlled release matrix tablets of Dyphylline using different types of polymers, and different preparation techniques such as direct compression, wet granulation, and hot melt methods. The prepared matrix tablets were evaluated by Infrared spectral analysis, differential thermal analysis, evaluation which included hardness, friability, content uniformity, and the in-vitro drug release. Kinetic analysis of the release profiles was investigated using different kinetic orders. All Dyphylline formulae obey Higuchi’s diffusion model. The diffusion is the mechanism of Dyphylline release from its controlled matrix tablets. IR and DSC revealed no incompatibility between Dyphylline and the polymers used in the prepared formulae. The obtained results revealed that the wet granulation technique using water as the granulating liquid is the best method for the formulation of Dyphylline hydrophilic matrix tablets compared with the other techniques. The high content of polymers led to the high value of T1/2, and a decrease in Dyphylline's extent due to the improvement of the retention of drug release. A synergistic effect was obtained using PVP-K-25 in the hydrophilic matrix tablets, which led to the retention of the drug release.

Dispersion of Nano-materials in Polymer Composite Materials

Polymer composites materials are the subject of extensive studies because of their novel properties compared with their constituent materials. Dispersion stability of sub-micron sized particles in the medium is important from the point of colloidal views. In the present study, dispersion of nano-materials in the matrix polymer is one of the most important problems to enhance their mechanical properties. We tackled this problem to carry out surface modification of the nano-materials, such as carbon nano tubes (CNTs), using amphiphilic polymers, polyNvinylacetamide (PNVA), synthesized thorough radical polymerization. Hydrogen bond worked between PNVA onto the modified nano-materials and hydrophilic matrix, such as polyvinyl alcohol (PVA), to enhance surface adhesions and dispersions of the nano-materials in the matrix. As a result, the mechanical properties of their composites materials were strengthened. When CNTs were used in PVA, the transparency of the composite was also increased due to improvement of their dispersions. In addition, if the CNTs formed the networks in the composites, the highly conductive and transparent polymer composite films were fabricated.

IVIVC for Extended Release Hydrophilic Matrix Tablets in Consideration of Biorelevant Mechanical Stress

Purpose When establishing IVIVC, a special problem arises by interpretation of averaged in vivo profiles insight of considerable individual variations in term of time and number of mechanical stress events in GI-tract. The objective of the study was to investigate and forecast the effect of mechanical stress on in vivo behavior in human of hydrophilic matrix tablets. Methods Dissolution profiles for the marketed products were obtained at different conditions (stirring speed, single- or repeatable mechanical stress applied) and convoluted into C-t profiles. Vice versa, published in vivo C-t profiles of the products were deconvoluted into absorption profiles and compared with dissolution profiles by similarity factor. Results Investigated hydrophilic matrix tablets varied in term of their resistance against hydrodynamic stress or single stress during the dissolution. Different scenarios, including repeatable mechanical stress, were investigated on mostly prone Seroquel® XR 50 mg. None of the particular scenarios fits to the published in vivo C-t profile of Seroquel® XR 50 mg representing, however, the average of individual profiles related to scenarios differing by number, frequency and time of contraction stress. When different scenarios were combined in different proportions, the profiles became closer to the original in vivo profile including a burst between 4 and 5 h, probably, due to stress-events in GI-tract. Conclusion For establishing IVIVC of oral dosage forms susceptible mechanical stress, a comparison of the deconvoluted individual in vivo profiles with in vitro profiles of different dissolution scenarios can be recommended.

Development of a Multifunctional Bioerodible Nanocomposite Containing Metronidazole and Curcumin to Apply on L-PRF Clot to Promote Tissue Regeneration in Dentistry

Teeth extractions are often followed by alveolar bone reabsorption, although an adequate level of bone is required for reliable rehabilitations by dental implants. Leukocyte and platelet-rich fibrin (L-PRF) has been widely applied in regenerative procedures and with antibiotic and antioxidant agents could play an essential role in hard and soft tissue healing. In this work, a nanocomposite (Sponge-C-MTR) consisting of a hyaluronate-based sponge loaded with metronidazole (MTR) and nanostructured lipid carriers containing curcumin (CUR-NLC) was designed to be wrapped in the L-PRF™ membrane in the post-extraction sockets and characterized. CUR-NLCs, obtained by homogenization followed by high-frequency sonication of the lipid mixture, showed loading capacity (5% w/w), drug recovery (95% w/w), spherical shape with an average particle size of 112.0 nm, and Zeta potential of −24 mV. Sponge-C-MTR was obtained by entrapping CUR-NLC in a hydrophilic matrix by a freeze-drying process, and physico-chemical and cytocompatibility properties were evaluated. Moreover, the aptitude of CUR and MTR to the penetrate and/or permeate both L-PRF™ and porcine buccal tissue was assessed, highlighting MTR penetration and CUR accumulation promoted by the system. The results positively support the action of nanocomposite in dental tissues regeneration when applied together with the L-PRF™.