Purpose: Zein is a biopolymer with a wide variety of industrial applications, recently proposed as controlling release excipient for the preparation of matrices. Aim of this work is to evaluate the effect of formulation parameters and tablets mechanical properties on the release performance of tramadol matrices prepared by direct compression. Methods: 100 mg tablets containing zein, silicified microcrystalline cellulose (SMCC), tramadol HCl and magnesium stearate, were prepared using rotary tablet press (Riva Piccola, Ronchi, IT) equipped with 6 mm diameter, round, flat-faced punches and operating at a rotation speed of 20 rpm. Several batches were prepared varying the drug loading, zein/SMCC ratio and the tablets hardness. All the prepared batches were analysed in term of dissolution behaviour and tablets swelling. Dissolution tests were performed at 37 ± 0.5 °C in a USP dissolution apparatus 1 (AT7 smart, Sotax, CH) using 500 ml of 0.1 N HCl (pH 1) for 2 h, followed by 4 subsequent hours in 50 mM phosphate buffer (pH 6.8). Tablets swelling was carried out positioning a matrix vertically in a glass Petri dish and adding 70 mL of the same media used for the dissolution studies. Images were recorded at different time intervals and analysed to determine the percentage of size variation. Results: The three investigated parameters showed a strong influence on the tramadol release. By increasing tablets hardness, the drug release slowed down, with an increase of the time necessary for the release of the 50% of the drug (tDR50) of around 450%. Similar tDR50 variation was also observed when the ratio zein/SMCC (total amount in the formulation 70%) moved from 1:2 to 2:1. Tramadol drug loading displayed the most evident effect. In fact, at 50% of drug loading the matrices showed a release behaviour characteristic of conventional release tablets, while for lower loading prolonged release profiles were observed. In these cases, a reduction of tramadol from 40 to 10% determined a tDR50 increase of around 350%. In most of the cases, the reduction of drug dissolution rate was related to a slower tablet swelling, which depends on the specific chemical features of the formulation components and on the porosity of the matrices. Conclusions: This study suggests that zein/SMCC represents a versatile platform to produce direct compressed matrices where the drug release can be modulated to the desired extent by simply adjusting certain formulation parameters. Thus, it could represent an alternative to more traditional monolithic matrix dosage forms (e.g. HPMC-based).

Controlling tramadol release using zein based matrices

Perinelli Diego Romano;Logrippo Serena;Pavoni Lucia;
2016-01-01

Abstract

Purpose: Zein is a biopolymer with a wide variety of industrial applications, recently proposed as controlling release excipient for the preparation of matrices. Aim of this work is to evaluate the effect of formulation parameters and tablets mechanical properties on the release performance of tramadol matrices prepared by direct compression. Methods: 100 mg tablets containing zein, silicified microcrystalline cellulose (SMCC), tramadol HCl and magnesium stearate, were prepared using rotary tablet press (Riva Piccola, Ronchi, IT) equipped with 6 mm diameter, round, flat-faced punches and operating at a rotation speed of 20 rpm. Several batches were prepared varying the drug loading, zein/SMCC ratio and the tablets hardness. All the prepared batches were analysed in term of dissolution behaviour and tablets swelling. Dissolution tests were performed at 37 ± 0.5 °C in a USP dissolution apparatus 1 (AT7 smart, Sotax, CH) using 500 ml of 0.1 N HCl (pH 1) for 2 h, followed by 4 subsequent hours in 50 mM phosphate buffer (pH 6.8). Tablets swelling was carried out positioning a matrix vertically in a glass Petri dish and adding 70 mL of the same media used for the dissolution studies. Images were recorded at different time intervals and analysed to determine the percentage of size variation. Results: The three investigated parameters showed a strong influence on the tramadol release. By increasing tablets hardness, the drug release slowed down, with an increase of the time necessary for the release of the 50% of the drug (tDR50) of around 450%. Similar tDR50 variation was also observed when the ratio zein/SMCC (total amount in the formulation 70%) moved from 1:2 to 2:1. Tramadol drug loading displayed the most evident effect. In fact, at 50% of drug loading the matrices showed a release behaviour characteristic of conventional release tablets, while for lower loading prolonged release profiles were observed. In these cases, a reduction of tramadol from 40 to 10% determined a tDR50 increase of around 350%. In most of the cases, the reduction of drug dissolution rate was related to a slower tablet swelling, which depends on the specific chemical features of the formulation components and on the porosity of the matrices. Conclusions: This study suggests that zein/SMCC represents a versatile platform to produce direct compressed matrices where the drug release can be modulated to the desired extent by simply adjusting certain formulation parameters. Thus, it could represent an alternative to more traditional monolithic matrix dosage forms (e.g. HPMC-based).
2016
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/406833
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