Desktop 3D printing of controlled release pharmaceutical bilayer tablets

Three dimensional (3D) printing was used as a novel medicine formulation technique for production of viable tablets capable of satisfying regulatory tests and matching the release of standard commercial tablets. Hydroxypropyl methylcellulose (HPMC 2208) (Methocel™ K100M Premium) and poly(acrylic acid) (PAA) (Carbopol® 974P NF) were used as a hydrophilic matrix for a sustained release (SR) layer. Hypromellose® (HPMC 2910) was used as a binder while microcrystalline cellulose (MCC) (Pharmacel® 102) and sodium starch glycolate (SSG) (Primojel®) were used as disintegrants for an immediate release (IR) layer. Commercial guaifenesin bi-layer tablets (GBT) were used as a model drug (Mucinex®) for this study. There was a favourable comparison of release of the active guaifenesin from the printed hydrophilic matrix compared with the commercially available GBT. The printed formulations were also evaluated for physical and mechanical properties such as weight variation, friability, hardness and thickness as a comparison to the commercial tablet and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). All formulations (standard tablets and 3D printed tablets) showed Korsmeyer-Peppas n values between 0.27 and 0.44 which indicates Fickian diffusion drug release through a hydrated HPMC gel layer

Experimental and modeling study of drug release from HPMC-based erodible oral thin films

In this work hydroxypropyl methylcellulose (HPMC) fast-dissolving thin films for oral administration are investigated. Furosemide (Class IV of the Biopharmaceutical Classification System) has been used as a model drug for in vitro release tests using three different set-ups: the Franz cell, the millifluidic flow-through device, and the paddle type dissolution apparatus (USP II). In order to enable drug incorporation within HPMC films, a multifunctional excipient, hydroxypropyl- β -cyclodextrin (HP- β -CD) has been included in the formulation, and the influence of HP- β -CD on film swelling, erosion, and release properties has been investigated. Mathematical models capable of describing the swelling and release processes from HPMC erodible thin films in different apparatuses have been developed. In particular, we propose a new model for the description of drug transport and release in a Franz cell that accounts for the effect of the unavoidable imperfect mixing of the receptor chamber

Ensaio de dissolução das formas farmacêuticas: aplicações na investigação científica e na Indústria Farmacêutica

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas.Os ensaios de dissolução são uma ferramenta importante em diversas etapas da Indústria Farmacêutica. Contudo, o devido reconhecimento e importância deste ensaio ocorreu há cerca de 50 anos atrás, com a consciencialização e comprovação de que a dissolução do fármaco é um fator crucial na biodisponibilidade do mesmo. Na Indústria Farmacêutica e nas diversas etapas de pesquisa, desenvolvimento e otimização de novas formas farmacêuticas, os ensaios de dissolução demonstram ser relevantes na seleção de uma composição farmacológica ideal, na caracterização biofarmacêutica do medicamento, no controlo de qualidade do fármaco nos períodos de produção, armazenamento e transporte, na caracterização do perfil de dissolução, entre outros. Inicialmente, estes ensaios foram desenvolvidos para avaliar a velocidade e o perfil de dissolução de formas farmacêuticas sólidas, contudo atualmente já são aplicados a sistemas transdérmicos, suspensões, supositórios, preparações semi-sólidas, aerossóis e outros. O ensaio de dissolução pretende prever o comportamento cinético do fármaco em condições fisiológicas simuladas, estabelecendo correlações in vitro-in vivo ou até mesmo a similaridade entre diferentes formas farmacêuticas, tudo isto com o auxílio de alguns modelos matemáticos de comparação de perfis de dissolução. Dissolution tests are an important tool in several stages of the Pharmaceutical Industry. However, its importance was acknowledged about 50 years ago, with awareness and evidence that the drug dissolution is a crucial factor in drug’s bioavailability. In the Pharmaceutical Industry and in the different stages of research, development and optimization of novel dosage forms, dissolution testing proves to be relevant for example: in the selection of an ideal pharmaceutical composition, in the characterizing of the biopharmaceutical medicine, in the control of drug quality in phases of production, storage and transportation, in characterization of the dissolution profile. These experiments were originally developed to evaluate the rate and dissolution profile of solid dosage forms, however dissolution tests are currently applied to transdermal patches, suspensions, suppositories, semisolid preparations, aerosols and others pharmaceutical dosage forms. Through the dissolution test, it could predict the behavior of the drug under simulated physiological and establish in vitro-in vivo correlations or even similarity among dosage forms, with the aid of some comparison mathematical models of dissolution profiles

Ensaio de dissolução das formas farmacêuticas: aplicações na investigação científica e na indústria farmacêutica

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas.Os ensaios de dissolução são uma ferramenta importante em diversas etapas da Indústria Farmacêutica. Contudo, o devido reconhecimento e importância deste ensaio ocorreu há cerca de 50 anos atrás, com a consciencialização e comprovação de que a dissolução do fármaco é um fator crucial na biodisponibilidade do mesmo. Na Indústria Farmacêutica e nas diversas etapas de pesquisa, desenvolvimento e otimização de novas formas farmacêuticas, os ensaios de dissolução demonstram ser relevantes na seleção de uma composição farmacológica ideal, na caracterização biofarmacêutica do medicamento, no controlo de qualidade do fármaco nos períodos de produção, armazenamento e transporte, na caracterização do perfil de dissolução, entre outros. Inicialmente, estes ensaios foram desenvolvidos para avaliar a velocidade e o perfil de dissolução de formas farmacêuticas sólidas, contudo atualmente já são aplicados a sistemas transdérmicos, suspensões, supositórios, preparações semi-sólidas, aerossóis e outros. O ensaio de dissolução pretende prever o comportamento cinético do fármaco em condições fisiológicas simuladas, estabelecendo correlações in vitro-in vivo ou até mesmo a similaridade entre diferentes formas farmacêuticas, tudo isto com o auxílio de alguns modelos matemáticos de comparação de perfis de dissolução. Dissolution tests are an important tool in several stages of the Pharmaceutical Industry. However, its importance was acknowledged about 50 years ago, with awareness and evidence that the drug dissolution is a crucial factor in drug’s bioavailability. In the Pharmaceutical Industry and in the different stages of research, development and optimization of novel dosage forms, dissolution testing proves to be relevant for example: in the selection of an ideal pharmaceutical composition, in the characterizing of the biopharmaceutical medicine, in the control of drug quality in phases of production, storage and transportation, in characterization of the dissolution profile. These experiments were originally developed to evaluate the rate and dissolution profile of solid dosage forms, however dissolution tests are currently applied to transdermal patches, suspensions, suppositories, semisolid preparations, aerosols and others pharmaceutical dosage forms. Through the dissolution test, it could predict the behavior of the drug under simulated physiological and establish in vitro-in vivo correlations or even similarity among dosage forms, with the aid of some comparison mathematical models of dissolution profiles

Buccal and topical drug delivery

The aim of this work is to investigate new and classical techniques, methods and formulations for topical and buccal release. All the formulations proposed are based on natural and biocompatible polymer matrices such as gellan gum, scleroglucan and hydroxypropylmethylcellulose. The proposed formulations are tested by in vitro release tests. In fact they represents a valid support and a useful starting point for the realization of a potentially usable in-vivo pharmaceutical formulation that may have commercial utility. The research work is both experimental and theoretical. Each topic presents a more chemical-pharmaceutical part, based on the formulation preparation and release experiments, and a more theoretical-numerical approach that allows a correct interpretation and description of the experimental data obtained. Release from hydrogels and thin films require different modelling approaches. Also the physico-mathematical description of different release experiments (different release devices such as Franz cell, millifluidic device and USP II) requires different theoretical and numerical techniques. The outcome of an accurate model development is of fundamental importance for future design of pharmaceutical formulations with prescribed release properties. In addition the formulations are investigated through rheological, mechanical, thermoanalytic and mucoadhesive tests in order to have a more comprehensive picture of their practical utilization