Biomedical subjects

M E Gil-Alegre

Publications and source records attributed to M E Gil-Alegre.

5 recordsLinked to original sources

PubMed2004

Statistical method for evaluation of dissolution stability in the formulation development of solid dosage forms: tablets of amonafide.

A statistical method for the evaluation of the dissolution stability results and for selecting the most stable formulation within a solid dosage form development is discussed. Three types of tablets of an antineoplastic drug, amonafide, stored at a relative humidities (RH), 45% and 75%, were used. The drug release from tablets was tested before and after storage. The experimental data were statistically fitted to empirical model equations. Furthermore, the best mathematical fit was the statistical comparison of the residuals. From the selected model equation, time-dependent dissolution (Q45 and DE45) and dissolved quantity-dependent parameters (t70, t100 and MDT) were calculated. A useful parameter to present and evaluate the results obtained in comparative stability studies was defined: the Modification Factor (MF). It allowed the selection of the most stable formulation in the easiest and fastest way: the most stable formulation should present the smallest modification of the studied characteristics, in other words, the smallest MF value. In this way, tablets II (manufactured by wet granulation and with Emcompress as main excipient) showed the greater dissolution stability of the three types of tablets studied. Amonafide tablets must be packaged in impermeable containers, since the environmental relative humidity strongly modifies their dissolution characteristics.

Adenine↗

PubMed2001

Statistical evaluation for stability studies under stress storage conditions.

During the pharmaceutical development of a new drug, it is necessary to select as soon as possible the formulation with the best stability characteristics. The current International Commission for Harmonisation (ICH) regulations regarding stability testing requirements for a Registration Application provide the stress testing conditions with the aim of assessing the effect of severe conditions on the drug product. In practice, the well-known Arrhenius theory is still used to make a rapid stability prediction, to estimate a drug product shelf life during early stages of its pharmaceutical development. In this work, both the planning of a stress stability study to obtain a correct stability prediction from a temperature extrapolation and the suitable data treatment to discern the reliability of the stability results are discussed. The study was focused on the early formulation step of a very stable drug, Mitonafide (antineoplastic agent), formulated in a parenteral solution and in tablets. It was observed, for the solid system, that the extrapolated results using Arrhenius theory might be statistically good, but far from the real situation if the stability study is not designed in a correct way. The statistical data treatment and the stress-stability test proposed in this work are suitable to make a reliable stability prediction of different formulations with the same drug, within its pharmaceutical development.

Antineoplastic Agents↗

PubMed2001

Procedure to evaluate the stability during processing and storage of a medicated premix and medicated farm feed: erythromycin thiocyanate.

In this paper, a stability study of a medicated premix and medicated farm feed containing erythromycin thiocyanate was planned. No drug degradation was detected during the medicated farm feed processing. In the medicated premix stability study, significant drug degradation was detected only at 40 degrees C and 75% relative humidity. Because after 2 years of storage at 25 degrees C and 60% relative humidity no degradation of erythromycin thiocyanate was detected, this period of time is proposed as the premix shelf life. In the medicated farm feed stability study, drug degradation was detected under accelerated conditions, but it was not detected under long-term storage conditions for 3 months. Therefore, the proposed shelf life of the medicated farm feed is 3 months, as this is time enough to be consumed. The planned stability study-storage conditions, testing frequency, and proposed data evaluation-allowed an easy and reliable evaluation of veterinary medicine stability.

Animal Feed↗

PubMed2000

Stability study of a sulfadimidine-containing medicated premix and its mixture with farm feed.

The objective of this paper was to study the stability of a medicated premix and a medicated farm feed containing sulfadimidine as the active ingredient. The medicated premix is supplied as powdered form and administered orally after mixing with animal feed. The sulfadimidine analytical method described in United States Pharmacopoeia 23 cannot be used to carry out the stability study because of its lack of specificity for different degradation products. Therefore, a high-performance liquid chromatography method was developed to assay sulfadimidine. This method was optimized and validated for the stability study. According to International Committee Harmonization (ICH) guidelines, the samples were stored under long-term testing and accelerated conditions for the stability study of the premix and the medicated farm feed. Sulfadimidine degradation was not detected in either form under any of the conditions studied.

Animal Feed↗

PubMed1999

Microbiological bioassay of erythromycin thiocyanate: optimisation and validation.

The validation of an analytical method for the quantitative determination of erythromycin thiocyanate formulated in an antibiotic preparation for veterinary use was carried out. This method is based on the microbiological method described in the European Pharmacopoeia to analyze erythromycin thiocyanate as a raw material. This erythromycin thiocyanate preparation is presented as a powder for oral administration after mixing with feed. For that reason, it was planned to validate the method for the quantitative determination of erythromycin thiocyanate incorporated both in the medicated premix and the mixture with feed. The microbiological method followed a linear model and was not proportional. The number of replicates needed to obtain a valid result was less than four in all cases. The small difference in concentration, expressed in natural logarithm detected by the method, was 0.1.

Administration, Oral↗