In vitro dissolution testing of matrix tablets containing tramadol hydrochloride

Tato diplomová práce se zabývá disolučním testováním lipofilních, hydrofilních a kombinovaných matricových tablet s tamadol hydrochloridem, kde jako lipofilní retardující složka byl zvolen glycerol-dibehenát (Compritol) a hydrofilní složkou byla hypomelosa (Methocel). V případě směsné matrice je použita kombinace obou retardujících komponent. Je studován vliv alkoholu na rychlost uvolňování tramadol hydrochloridu z tablety. Matricové tablety byly zhotoveny přímým lisováním, kde jako plnidlo byla použita mikrokrystalická celulóza (Prosolv) a jako lubrikant umožňující lisování byl zvolen stearát hořečnatý. Disoluční testy byly prováděny při 37°C v kyselém disolučním médiu o pH 1,2. a disolučním médiu s obsahem 40 obj. % ethnaolu. Získané disoluční profily byly matematicky vyhodnoceny na základě nelineární regresní analýzy. Nakonec byl diskutován vliv alkoholu na rychlost uvolňování tamadol hydrochloridu z jednotlivých typů matric.This master thesis is focused on disolution testing of liphophilic, hydrophilic and combined matrix tablets with tramadol hydrochloride. As a lipophilic excipient was used glycerole-dibehenate (Compritol) and hydrophilic component was formed by hypromelose (Methocel). In case of combined matrix, a mixture of both retarding components was used.In addition, effect of alcohol on dissolution rate of tramadol hydrochloride from matrices was studied. Matrix tablets were prepared by direct compresion, where a silicifed microcrystalline cellulose has been chosen as binder-filler. Magnesium-stearate was a lubricant enabling the compression. Dissolution tests were carried out at temperature 37°C in acidic medium (pH 1,2) and next with acidic medium containing 40 vol.% of ethanole. Obtained dissolution profiles were mathematically evaluated by nonlinear-regression analysis. Influence of alcohol on dissoluton rate of tramadol hydrochloried has been discussed at the end.Fakulta chemicko-technologickáDiplomant přednesl obhajobu diplomové práce a odpověděl otázky komise: Uveďte struktury použitých excipientů (doc. Čičmanec) Jak alkohol ovlivňuje rychlost uvolňování tramadol hydrochloridu? (doc. Skopal

Determination of verapamil hydrochloride solubility in aqueous solutions depending on temperature

Tématem této bakalářské práce je studium teplotní závislosti rozpustnosti verapamil hydrochloridu pro vodné roztoky lišící se pH a iontovou silou (voda, roztok o pH 1,2 simulující žaludeční šťávy a octanový pufr o pH 4,5). Teoretická část pohlíží na rozpustnost z různých aspektů a zabývá se experimentálním stanovením rozpustnosti léčivých látek. Předmětem experimentální části je srovnání dvou metod, pomocí kterých byla měřena rozpustnost verapamil hydrochloridu v rozmezí teplot 25-40°C. Dále byl studován vliv iontů na rozpustnost dané látky. Získaná data byla statisticky zpracována.The aim of this bachelor thesis is study of verapamil hydrochloride´s solubility depending on temperature in various aqueous solutions of different pH values and ionic strength (water solution, pH 1,2 solution simulating gastric juice and pH 4,5 acetic buffer). Theory of this work focuses on solubility from different aspects and also deals with experimental determination of drugs solubility. The subject of the experimental part is comparison of two measuring solubility methods in the temperature range from 25 to 40°C. Then was also studied the influence of ions on the drug´s solubility. Obtained data were statistically processed.Fakulta chemicko-technologick

kritický přehled FDA a EMA statistických metod pro srovnání in vitro disolučních profilů farmaceutických produktů

A drug dissolution profile is one of the most critical dosage form characteristics with immediate and controlled drug release. Comparing the dissolution profiles of different pharmaceutical products plays a key role before starting the bioequivalence or stability studies. General recommendations for dissolution profile comparison are mentioned by the EMA and FDA guidelines. However, neither the EMA nor the FDA provides unambiguous instructions for comparing the dissolution curves, except for calculating the similarity factor f(2). In agreement with the EMA and FDA strategy for comparing the dissolution profiles, this manuscript provides an overview of suitable statistical methods (CI derivation for f(2) based on bootstrap, CI derivation for the difference between reference and test samples, Mahalanobis distance, model-dependent approach and maximum deviation method), their procedures and limitations. However, usage of statistical approaches for the above-described methods can be met with difficulties, especially when combined with the requirement of practice for robust and straightforward techniques for data evaluation. Therefore, the bootstrap to derive the CI for f(2) or CI derivation for the difference between reference and test samples was selected as the method of choice.</p>Disoluční profil léčiva je jedním z hlavních kritérií charakterizujících léčiva ve formě tablet. Srovnání disolučních profilů odlišných farmaceutických produktů hraje klíčovou roli před začátkem studií biodostupnosti a stability

3D-tištěný povlak matricových tablet s prodlouženým uvolňováním: Účinný nástroj pro prevenci alkoholem indukovaných ztrát léčiva

Tablets used for extended drug release commonly contain large amounts of drugs. The corresponding drug release mechanism thus has to be well-known and invariable under numerous conditions in order to prevent any uncontrolled drug release. Particularly important is the stability and invariability of the release mechanism in the presence of alcohol due to the possible occurrence of the dose dumping effect. The effect of 3D printing (3DP) coating on the drug release mechanism and the drug release rate was studied as a possible tool for the prevention of the alcohol-induced dose dumping effect. Three types of matrix tablets (hydrophilic, lipophilic, and hydrophilic-lipophilic) were prepared by the direct compression method and coated using 3DP. The commercial filament of polyvinyl alcohol (PVA) and the filament prepared from hypromellose by hot melt extrusion (HME) were used as coating materials. Both coating materials were characterized by SEM, DSC, Raman spectroscopy, and PXRD during particular stages of the processing/coating procedure. The dissolution behavior of the uncoated and coated tablets was studied in the strongly acidic (pH 1.2) and alcoholic (40% of ethanol) dissolution media. The dissolution tests in the alcoholic medium showed that the Affinisol coating was effective in preventing the dose dumping incidence. The dissolution tests in the acidic dissolution media showed that the Affinisol coating can also be useful for the delayed release of active substances.Tablety používané pro prodloužené uvolňování běžně obsahují rozsáhlé množství léčiv. Z toho důvodu je třeba zabránit nekontrolovanému uvolˇbnování léčiva vedoucímu ke ztrátám. Tyto ztráty bývají často způsobeny přítomností alkoholu

Vliv alkoholu na ionizující a neionizující léčiva uvolňovaná z hydrofilních, lipofilních a duálních matric

The aim of this work was to investigate and quantitatively evaluate the effect of presence of alcohol on in vitro release of ionizing and non-ionizing drug from hydrophilic, lipophilic and hydrophilic-lipophilic matrix tablets. The Food and Drug Administration (FDA) recommends in vitro dissolution testing of extended release formulations in ethanolic media up to 40% because of possible alcohol-induced dose dumping effect. This study is focused on comparison of the dissolution behavior of matrix tablets (based on hypromellose and/or glyceryl behenate as retarding agent) of the same composition containing different type of drug - ionizing tramadol hydrochloride (TH) and non-ionizing pentoxifylline (PTX). The dissolution tests were performed in acidic medium (pH 1.2) and in alcoholic medim (20%, 40% of ethanol) and the changes of tablets were observed also photographically. It was found that the alcohol resistence of the hydrophilic-lipophilic formulations with TH and the hydrophilic-lipophilic formulations with PTX containing a higher amount of hypromellose does not reflect the alcohol resistence of the formulations with pure hypromellose or glyceryl behenate. Both hydrophilic-lipophilic formulation with TH and more lipophilic formulation with PTX show significant alcohol dose dumping effect. (C) 2019 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.Cílem práce bylo studium vlivu přítomnosti alkoholu při uvolňování léčiv z hydrofilních, lipofilních i duálních matric

Matrix Tablets Based on Chitosan–Carrageenan Polyelectrolyte Complex: Unique Matrices for Drug Targeting in the Intestine

The present study focused on the more detailed characterization of chitosan–carrageenan-based matrix tablets with respect to their potential utilization for drug targeting in the intestine. The study systematically dealt with the particular stages of the dissolution process, as well as with different views of the physico-chemical processes involved in these stages. The initial swelling of the tablets in the acidic medium based on the combined microscopy–calorimetry point of view, the pH-induced differences in the erosion and swelling of the tested tablets, and the morphological characterization of the tablets are discussed. The dissolution kinetics correlated with the rheological properties and mucoadhesive behavior of the tablets are also reported, and, correspondingly, the formulations with suitable properties were identified. It was confirmed that the formation of the chitosan–carrageenan polyelectrolyte complex may be an elegant and beneficial alternative solution for the drug targeting to the intestine by the matrix tablet

Nový přístup k managmentu disolučních testů a získání kinetických a termodynamických dat:: Uvolňování modelového léčiva z matricové tablety založené na glyceryl behenátu

This study is focused on the use of glyceryl behenate as a lipophilic excipient of matrix tablets providing controlled drug release. The aim of this study is to evaluate activation energy (EA) and changes of the thermodynamic parameters (Delta H, Delta S, Delta G) of a dissolution process. These values, which have not yet been published, can lead to better understanding of a drug release mechanism and can extend the use options of glyceryl behenate in the pharmaceutical industry. Values of Delta H, Delta S, Delta G and E-A, providing an overall thermodynamic view on the studied matrix tablets, are evaluated based on the temperature-dependences of the release rate constant of a model drug (temperature range 25 - 45 degrees C). The studied lipophilic matrix tablets contain 10% to 50% of glyceryl behenate. Dissolution testing is carried out in an aqueous solution of HCl with addition of NaCl (pH1.2). Positive values of Delta H in the range of 3.83 to 56.13 kJ mol(-1) and positive values of Delta G indicate that the dissolution of the studied glyceryl behenate matrix tablets is an endothermic process which does not proceed spontaneously (in a temperature range of 25 - 45 degrees C). The negative slope of the linear curves of enthalpy-entropy compensation confirms the entropy-driven dissolution.Studie je zaměřena na použití glyceryl behenátu jako lipofilního excipientu matricové tablety s prodlouženým uvolňováním. Cílem studie byl vývoj aktivační energie a změn termodynamických paramaetrů disolučního procesu