ObtenÃÃo, caracterizaÃÃo e avaliaÃÃo microbiolÃgica de uma nova forma farmacÃutica contendo hidroquinona

AUTOR(ES)
DATA DE PUBLICAÇÃO

2003

RESUMO

Hydroquinone (HQ) is a drug reported to possess manifold biological activities, such as depigmenting, antimicrobial and antitumour properties. The PluronicLecithin Organogel (PLOme) is a phospholipidic microemulsion particularly implied when a high cutaneous permeability and systemic absorption of a drug is suitable. Once that HQ is highly unstable into various topical vehicles and it presents low topical bioavailability and toxicity, the HQ appears as a fulfilling drug to this liposomal pharmaceutical form. The aim of this work was therefore to incorporate such a drug into this transdermal drug delivery system. Furthermore, the stability and the kinetic profile as well as the antimicrobial activity of both free and incorporated forms of HQ were evaluated. HQ-loaded PLOme and unloaded PLOme were prepared according to the supplier directions. The samples were then submitted to accelerate and long-term stability tests. Thermal stability studies were also performed monitoring the pH and the HQ content into PLOme formulations stored at 25oC and 37oC. The HQ content was assayed by high performance liquid chromatography using the United States Pharmacopoeia method. A method of drug extraction from PLOme formulations was developed and validated. The in vitro HQ kinetic profile from the best formulations at 0.1% concentration was examined using the Franz cells method. A cellulose membrane was used to separate the donors and the aqueous receptor medium. The antimicrobial activity against ATCC and resistant Staphylococcus aureus strains was determined for free and encapsulated HQ forms (Staphylococcus aureus ATCC chosen were the ATCC 6538/ FDA 209 and the ATCC 6538P/ FDA 209P). The multi inoculation agar dilution susceptibility testing method were used. No microscopic or microscopic alterations were detected after accelerated stability testing, but the presence of darkness of HQ loaded PLOme. Long-term stability testing also revealed darkness for HQ-loaded formulations. Neither detectable increase on the particle size nor modification on particle shape occurred until 120 days. No relevant pH evolution was observed for both HQ-free and HQ-loaded PLOme. Concerning the HQ content, no degradation was noticed under unfavorable thermal conditions. The pH changes were not detected in the short-term thermal stability analysis. In contrast, the long-term stability showed a second-order HQ degradation, which leads to a short shelf life. The HQ rate obtained from microemulsion was close to 1.5 times lower than that one derived with HQ in a gel matrix at a similar drug concentration. Free PLOme-encapsulated hydroquinone showed to have great in vitro inhibitory potential against strains of S. aureus (including multi resistant ones); PLOmeencapsulated hydroquinone had better activity than hydroquinone against two of the testing-strains.The transdermal gel containing HQ, otherwise, seems not to be enough stable under the above mentioned stability tests. As a consequence, further investigation is required on the stability and kinetic of this pharmaceutical form before commercialization

ASSUNTO(S)

estabilidade farmacia pluronic lecithin organogel (plome) p-diidroxibenzeno (hidroquinona)

ACESSO AO ARTIGO

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