Optimization and Evaluation of Felodipine Co-Crystals Embedded Buccal Film for Improving Bioavailability

The preformulation study of felodipine was carried out and it was found that the drug is poorly water soluble. The co-crystals were prepared using three different coformers sorbitol, ascorbic acid and oxalic acid. The solublity enhancement was observed in combination with sorbitol compared to other co-formers used. The characterization of co crystals was performed like PXRD, FTIR, SEM Analysis. XRD results indicates the amorphous form of the drug. The co-crystals were embedded within the buccal flim for sustained release of the drug. The buccal film was optimized by Factorial design using HPMC and PVA as independent variables. Two responses were chosen such as Drug permeation and Mucoadhesive strength for optimizing the buccal flim. Based on desirability value (1.00) the formulation factors were found and observed value is closer to the predicted values. This results reveals that the model is validated. The morphology of buccal flim was charactarized with SEM analysis. The buccal flim was tested for Thickness, weight variation, Folding Endurance, Drug content, Moisture loss, Surface pH and Swelling studies. The drug permeation kinetic study was performed in the optimized formulation and the results reveals that the mechanism of drug permeation follows diffusion from higher r2 value for Higuchi kinetics (r2 = 0.992) and the n value of peppas model (n=0.653)shows that the mechanism follows Non-Fickian diffusion. Novel Buccal adhesive cocrystal embedded patch offers innumerable advantages. While the water solubility of the drug is improved by 2 folds so that the permeation efficacy of the drug also improved, aided by increased bioavailability. Buccal patch exerts many advantages like ease of administration and withdrawal, avoiding first pass metabolism, low enzyme activity, enhancement of permeability and high patient compliance. Hence the novel formulation holds immense opportunities to be explored in terms of different drug candidates

AN ASSESSMENT ON BUCCAL MUCOADHESIVE DRUG DELIVERY SYSTEM

Buccal drug delivery system (BDDS) has won a variety of exposure and traction as it possesses plenty of advantages and benefits as evaluate to different mucosal drug delivery systems. Buccal path for systemic drug delivery, the use of mucoadhesive polymers twill significantly increase the efficacy of many tablets, has been of outstanding interest over the previous couple of decades. This article affords a precise of BDDS mechanisms, consisting of a composition of the oral mucosa, delivery mechanism, numerous forms of BDDS, formulation, assessment and application of BDDS. Additionally, this text affords a precis over the patents, advertised products and destiny factors of BDDS. In this evaluation article, we've got tried to assemble the maximum significant reports (1988 to 2021) of formulation, assessment, application, patents of BDDS. This review will help pharmaceutical researchers to clarify the potential of BDDS to overcome the various existing drug delivery dispute like the efficiency of absorption, permeability and bioavailability of drugs

MUCOADHESIVE BUCCAL FILMS: A NOVEL APPROACH FOR THE DELIVERY OF ANTI-HYPERTENSIVE DRUGS

The buccal drug delivery system is a prominent route of administration for drug delivery through the buccal mucosa. It is rich in blood supply with more surface area for rapid absorption as well as provides direct entry of drugs from the site of application into the systemic circulation through the jugular vein. Buccal drug delivery systems consist of various approaches such as lozenges, wafers, gels, microparticles, patches or films from which mucoadhesive buccal film is an attractive dosage form in terms of flexibility and high systemic bioavailability. Since most of the antihypertensive drugs show first-pass metabolism which leads to less oral bioavailability generally up to 20–50%. Thus, incorporation of antihypertensive drugs in mucoadhesive buccal films using mucoadhesive polymers can provide higher systemic bioavailability. The films can be formulated using various techniques such as solvent casting method and hot extrusion melt method. These films can be evaluated based on various characteristics to determine their efficacy and performance such as tensile strength, mucoadhesion residence time, and kinetic release data analysis. They have various advantages over conventional solid oral dosage forms, hence are preferable for the preparation of antihypertensive drug-loaded buccal films. Mucoadhesive buccal films of antihypertensive drugs can also provide controlled drug delivery with enhanced bioavailability

Fabrication of solid dispersion based patches using hot melt injection moulding and fused deposition modelling 3D printing

The poor aqueous solubility of many APIs, such as felodipine, are significant dissolution rate limiting factors that often lead to poor oral systemic bioavailability. Solid dispersions have been used as a formulation approach to improve drugs dissolution properties. Most of the reported solid dispersion formulations in the literature are binary mixtures with limited functionalities (with enhancing dissolution being the primary function). The aim of this study is to design, characterise and evaluate complex solid dispersions with intentionally designed microstructures (in the form of phase separations). The potential functionalities of these microstructures were explored by this project. In our view, the complex formulations are more representative of real pharmaceutical products in their final forms. HME-IM is a single processing technique for fabricating formulations with high geometric precision in a rapid, efficient and environmentally friendly way. It was used as the main processing method to produce the solid dispersion based buccal patches in this project. The patches were thoroughly characterised using conventional techniques including DSC, MTDSC, TGA, DVS, ATR-FTIR, PXRD, SEM, EDS, IR imaging, mucoadhesion and in vitro dissolution testing. In order to address the spatial distribution of the phase separations, two non-conventional characterisation methods, thermal analysis by structural characterisation and X-ray microcomputed tomography, were introduced to provide novel insights into the heterogeneity and phase distribution of these formulations. The results revealed that HME-IM patches with 10% drug loading were unsaturated while those with 20-30% w/w drug concentration were saturated or even supersaturated. HME-IM patches containing TPGS were more solubilising to felodipine and more stable compared to Tween 80 containing systems. Thermal analysis by structural characterisation provided rapid detection of heterogeneity and the thermal dissolution of crystalline drug fraction while XμCT provided microscale spatial distribution of different phases. Having shown the advantages of using polymeric blends to formulate solid dispersions that were demonstrated by the felodipine buccal patches, we further explored the use of polymer blends for improving the FDM 3D printability of pharmaceutical solid dosage forms with the potential applications in personalised medicine. This project demonstrated the potential and formulation principles of using HME-IM and FDM 3D printing as formulation methods for production of polymer blend based complex solid dispersions for the purposes of enhanced bioavailability of poorly soluble drugs and providing personalised medicines

Therapeutic and toxic blood concentrations of nearly 1,000 drugs and other xenobiotics

Introduction: In order to assess the significance of drug levels measured in intensive care medicine, clinical and forensic toxicology, as well as for therapeutic drug monitoring, it is essential that a comprehensive collection of data is readily available. Therefore, it makes sense to offer a carefully referenced compilation of therapeutic and toxic plasma concentration ranges, as well as half-lives, of a large number of drugs and other xenobiotics for quick and comprehensive information. Methods: Data have been abstracted from original papers and text books, as well as from previous compilations, and have been completed with data collected in our own forensic and clinical toxicology laboratory. The data presented in the table and corresponding annotations have been developed over the past 20 years and longer. A previous compilation has been completely revised and updated. In addition, more than 170 substances, especially drugs that have been introduced to the market since 2003 as well as illegal drugs, which became known to cause intoxications, were added. All data were carefully referenced and more than 200 new references were included. Moreover, the annotations providing details were completely revised and more than 100 annotations were added. Results: For nearly 1,000 drugs and other xenobiotics, therapeutic ("normal") and, if data were available, toxic and comatose-fatal blood-plasma concentrations and elimination half-lives were compiled in a table. Conclusions: In case of intoxications, the concentration of the ingested substances and/or metabolites in blood plasma better predicts the clinical severity of the case when compared to the assumed amount and time of ingestion. Comparing and contrasting the clinical case against the data provided, including the half-life, may support the decision for or against further intensive care. In addition, the data provided are useful for the therapeutic monitoring of pharmacotherapies, to facilitate the diagnostic assessment and monitoring of acute and chronic intoxications, and to support forensic and clinical expert opinions