CURCUMIN MICROENCAPSULATION USING CHITOSAN–ETHYL CELLULOSE–GMS MIXTURE FOR PRESERVATION OF MUCOADHESIVE PROPERTIES AND CONTROLLED RELEASE KINETIC

Objective: This research aimed to prepare curcumin microcapsules by the spray drying method and to evaluate their characteristics. Methods: The microcapsules were prepared by the spray drying method. The generated microcapsules were evaluated for organoleptic, morphology, particle size, the percentage of curcumin and water content. Furthermore, the release of curcumin from the microcapsules was tested in vitro and compared to uncoated curcumin powder. In addition, the mucoadhesive properties of uncoated curcumin powder and curcumin microcapsules were also evaluated. Results: The results showed that the microcapsules had spherical shape with particle size in the range of 100–1009 µm and water content of 9.34% (w/w) (FIII) and 8.09% (w/w) (FVI). The release of curcumin from its uncoated powder and the microcapsules FVI within 8 h were 8.87% and 26.32% (w/w), respectively. It was found that the mucoadhesive properties of microcapsules FVI were better than those of FIII and uncoated curcumin powder. Microcapsules FVI rendered the cumulative amount of curcumin remaining on the intestinal mucosa of 55% (w/w) within 3 h. Conclusion: Accordingly, curcumin microcapsules generated by spray drying could be further formulated into various solid dosage forms for a better therapeutic effect.

Study of the dissolution kinetics of drugs in solid dosage form with lisinopril and atorvastatin and intestinal permeability to assess their equivalence in vitro

Atorvastatin and lisinopril are a successful combination for the treatment of patients with chronic heart failure and hypertension. Study of the dissolution kinetics of drugs in solid dosage form with lisinopril and atorvastatin and intestinal permeability to assess their equivalence in vitro were described. In medium with hydrochloric acid pH 1.2, in the medium of acetate buffer solution with a pH of 4.5 and in the medium phosphate buffer solution with a pH of 6.8 for 15 min more than 85% of the active substance passes into solution, hence the dissolution profiles these drugs in these environments are similar, and the drugs in them are “very quickly soluble”. Among the in vitro models that make it possible to assess the degree of absorption of API, the most widely used culture of adenocarcinoma cells of the colon – Caco-2. The development of the analytical methodology and its validation is the final stage of both the dissolution study and the Caco-2 test, as well as the biowaver procedure. It plays the most important role in the reliability of the results for all the above procedures and tests. To study permeability, method LC-MS/MS was developed. According to the obtained results, atorvastatin and lisinopril showed low permeability. The values ​​of recovery of transport of test and control substances through the monolayer of cells of the Caco-2 line indicate that the results of the experiment can be considered reliable. The equivalence of the drugs “Lisinopril”, tablets of 10 mg and “Atorvastatin”, tablets of 10 mg, belongs to class III BCS proven by in vitro studies.

Mucilage of Coccinia grandis as an Efficient Natural Polymer-Based Pharmaceutical Excipient

Natural eco-friendly materials are recently employed in products to replace synthetic materials due to their superior benefits in preserving the environment. The herb Coccinia grandis is widely distributed in continents like Asia and Africa and used traditionally to treat fever, leprosy, asthma, jaundice, and bronchitis. Mucilage of Coccinia grandis was accordingly extracted, isolated by a maceration technique, and precipitated. The mucilage was evaluated for its physicochemical, binding, and disintegrant properties in tablets using paracetamol as a model drug. The crucial physicochemical properties such as flow properties, solubility, swelling index, loss on drying, viscosity, pH, microbial load, cytotoxicity was evaluated and the compatibility was analyzed using sophisticated instrumental methods (TGA, DTA, DSC, and FTIR). The binding properties of the mucilage was used at three different concentrations and compared with starch and PVP as examples of standard binders. The disintegrant properties of mucilage were used at two different concentrations and compared with standard disintegrants MCCP, SSG, and CCS. The tablets were punched and evaluated for their hardness, friability, assay, disintegration time, in vitro dissolution profiles. In vitro cytotoxicity studies of the mucilage were performed in a human embryonic kidney (HEK) cell line. The outcome of the study indicated that the mucilage had good performance compared with starch and PVP. Further, the mucilage acts as a better disintegrant than MCCP, SSG and CCS for paracetamol tablets. Use of a concentration of 3% or less demonstrated the ability of the mucilage to act as a super disintegrating agent and showed faster disintegration and dissolution, which makes it as an attractive, promising disintegrant in formulating solid dosage forms to improve the therapeutic efficacy and patient compliance. Moreover, the in vitro cytotoxicity evaluation results demonstrated that the mucilage is non-cytotoxic to human cells and is safe.

Recent Advances in the Excipients Used in Modified Release Vaginal Formulations

The formulation of an ideal vaginal drug delivery system (DDS), with the requisite properties, with respect to safety, efficacy, patient compliance, aesthetics, harmonization with the regulatory requirements, and cost, requires a meticulous selection of the active ingredients and the excipients used. Novel excipients defined by diversity and multifunctionality are used in order to ameliorate drug delivery attributes. Synthetic and natural polymers are broadly used in pharmaceutical vaginal formulations (solid, semi-solid dosage forms, implantable devices, and nanomedicines) with a promising perspective in improving stability and compatibility issues when administered topically or systemically. Moreover, the use of biopolymers is aiming towards formulating novel bioactive, biocompatible, and biodegradable DDSs with a controllable drug release rate. Overviewing vaginal microenvironment, which is described by variable and perplexed features, a perceptive choice of excipients is essential. This review summarizes the recent advances on the excipients used in modified vaginal drug delivery formulations, in an attempt to aid the formulation scientist in selecting the optimal excipients for the preparation of vaginal products.

PHARMACEUTICAL MARKET ASSORTMENT RESEARCH OF DRUGS FOR VAGINAL USE WITH PROBIOTIC MEDICINES DETAILING

vaginal route delivery of drugs is an integral part of gynaecological diseases treatment including different genesis vulvovaginitis. The aim of this study it to analyze Ukrainian pharmaceutical market assortment of drugs for vaginal use with probiotic medicines determination. The marketing research was conducted with using of analysis, synthesis, comparison, generalization, content-analysis, statistical, graphical methods. The data of State register of medicines (as of June, 30, 2021), register of wholesale dispensing prices for medicines (as of June, 30, 2021), official web-sites LLC «Morion», «Pharmacy.online», «Compendium.online» were used as objects of the study. As a result, it is determined that as of June 30, 2021 142 medicines for vaginal use are registered on Ukrainian pharmaceutical market with dosage forms, active substances doses, condition for dispensing consideration, 100 brand names, 26 international nonproprietary names, 7 synonymous names. Structural ATC-classification analysis has shown that medicines for vaginal use are included in ATC-groups G «Genito urinary system and sex hormones» and D «Dermatologicals» The assortment macrocontour is formed, it demonstrates that 67,2% of drugs for vaginal use are involved in group G01A «Аntiinfectives and antiseptics, excluding combinations with corticosteroids». More than 80% of drugs for vaginal use are registered as solid dosage forms, and almost half of them as suppositories or pessaries. Almost 65% of medicines are foreign, and 3/4 of them contain only active substance, more than 50% are prescription only medicines. For 44,4% drugs for vaginal use the storage period of 3 years (36 months) is determined. Detailing analysis of medicines with probiotic activity has shown assortment deficiency (only 3 brand names are registered). The liquidity coefficients calculations for this brand manes don’t allow to characterize these drugs as economically affordable. The obtained results of this study inform about the domestic drugs for vaginal use with probiotic activity development relevance, especially in pessaries as dominant dosage form on the pharmaceutical market.

Prediction of the composition of prolonged release tablets based on 4,4'-(propandiamido) sodium dibenzoate using the SeDeM method

Introduction. Direct compression technology is one of the most common tablet technologies. As known, many active pharmaceutical ingredients are not suitable for this technology without the addition of special excipients. A useful tool for determining the suitability of powdered materials for direct compression technology is the Sediment Delivery Model (SeDeM) method, based on the concept of Quality by Design. The presented method allows not only to assess the suitability of a material for direct compression, but also helps to predict the composition of a solid dosage form in the form of a tablet, which, in turn, leads to a significant reduction in experimental work carried out in the development of a new drug.Aim. Prediction of the compositions of matrix tablets based on sodium 4,4'-(propanediamido)dibenzoate with prolonged release, obtained by direct compression using the method of mathematical modeling SeDeM.Materials and methods. The objects of the study were the original substance sodium 4,4'-(propanediamido)dibenzoate, as well as a number of auxiliary substances, which included polymers used for dosage forms with prolonged release, a dusting component – magnesium stearate, and a filler – lactose monohydrate. Physicochemical and technological properties of APIs, explosives, obtained tablet mixtures and tablets were studied in accordance with the requirements of the State Pharmacopoeia of the Russian Federation XIV ed. and EP 9th ed.Results and discussion. The properties of the substance and excipients were assessed in accordance with the SeDeM method. It was found that the substance 4,4'-(propanediamido) sodium dibenzoate is not suitable for direct pressing due to poor flowability and low compressibility. Hypromellose Methocel K4M had good compressibility, but it did not have sufficient flowability. The other tested polymers had satisfactory properties for the direct compression technology. The composition of the tablet mixtures was calculated using the SeDeM method, the obtained tablet mixtures had satisfactory technological characteristics for obtaining tablets by direct compression. The tablets obtained as a result of the experiment also met the pharmacopoeial requirements.Conclusion. Prediction of the composition of sustained-release tablets based on the original substance sodium 4,4'-(propanediamido)dibenzoate was carried out using the SeDeM method. It was found that this method is suitable for the development of the composition of tablets based on sodium 4,4'-(propanediamido)dibenzoate.

Tandem Mass Spectrometry (MS/MS) in the Preclinical Pharmacokinetic Study of a Highly Prescribed SNRI Drug for Depression and Its Application to Oral Extended Release Solid Dosage Formulations in Rabbits

Preclinical pharmacokinetic (pK) studies in animal models during the formulation development phase give preliminary evidence and near clear picture of the pK behavior of drug and/or its dosage forms prior to clinical studies on humans and help in tailoring of the dosage form according to the expected and requisite clinical behavior. The present work reports first of its kind preclinical pK study on oral extended release (ER) solid dosage formulations of venlafaxine (VEN) in New Zealand White rabbits. The VEN is a highly prescribed and one of the safest and most effective therapeutic agents used in the treatment different types of depression disorders worldwide. The LC-MS/MS bioanalytical method developed for this purpose demonstrated enough reliability in simultaneously quantitating VEN and its equipotent metabolite O-desmethylvenlafaxine (ODV) in rabbit plasma. The method described uses solid phase extraction for sample preparation followed by an ultra-fast LC-MS/MS analysis. The chromatographic separation was achieved isocratically with a predominantly polar mobile phase by employing RPLC. The triple quadrupole LC/MS/MS system operated in MRM mode used an ESI probe as an ion source in positive polarity. The validation results are within the permissible limits of US FDA recommendations and acceptance criteria for bioanalytical method validation.