Artigo academico

1. Although each system offers an unlimited number of sample formulations, we selected a representative W/O and O/W formulation from system 1 to test transdermal delivery of hydrophilic and hydrophobic drugs across stripped human skin. The results (Table III) indicate that the O/W system provided significantly better flux for all the drugs studied (p < 0.025). The simultaneous delivery of estradiol with diltiazem HCl from the ME system did not affect the transport of either drug (p > 0.5, Table IV). Interestingly, the drug permeability from a homogenous single phase composed of all the water-soluble components is similar to drug flux from O/W ME (p > 0.25). This suggests that the oil phase in our formulation serves as a depot for the drug, while the drug transport occurs primarily from the water phase. This phenomenon could have significant implications for the development of transdermal systems for long-term sustained delivery.

1. For all the drugs tested, the ME systems provided sig-nificant enhancement (Table V). The finding that flux is im-proved in O/W formulations as compared with W/O systems even for the hydrophobic drugs suggests that transport from the aqueous phase is key. When the organic phase and sur-factants were removed from the ME, leaving only the water phase components (H2O, ethanol, NMP), the flux was com-parable to that from the O/W ME (Table IV). Previous work indicates that the H2O/NMP synergy provides greater trans-dermal flux enhancement than H2O/ethanol. Although the complexity of the multiple components in the system makes it difficult to determine the exact molecular interactions, it ap-pears that the presence of NMP in the water phase plays a key role in the transport of hydrophobic drugs from an O/W ME.

1. It has been suggested that ME transdermal enhancement is a result of increasing drug concentration in the donor phase (2). In our systems containing the chemical enhancer NMP, we believe that the effective permeability of the membrane is also affected. If enhancement is merely a concentration effect, then the permeability of drug across human skin should re-main constant. The permeability of all four drugs was com-pared from the ME systems against the solvent (IPM or H2O) in which they were most soluble (Table V). There is a clear permeability enhancement for both hydrophilic and hydro-phobic drugs from the ME systems (p < 0.001). This finding agrees with previous work where we found that NMP is ca-pable of improving permeability of drugs from both IPM and

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Effect of NMP on Lidocaine Partitioning

NMP is freely miscible in both H2O and IPM. It is also capable of improving lidocaine partitioning into the phase where the drug is less soluble (Fig. 2). The hydrophobic lido-caine free base partitions 2.6 times more in the aqueous phase with the addition of 33% v/v NMP. Similarly, the hydrophilic lidocaine HCl partitions 6.5 times more favorably in the IPM phase with the addition of 33% v/v NMP. The concentration of drug in the minority phase is improved 1.9-fold for lido-caine free base and 5.7-fold for lidocaine HCl. From these results, we conclude that NMP can act as a partition enhancer in ME systems. For a hydrophobic drug to transport from an O/W ME, the drug (e.g., lidocaine free base) must first par-tition from the “encapsulated” organic phase into the aque-ous phase to reach the skin. The presence of NMP in the system is able to increase the concentration of the hydropho-bic drug in the water phase, making it available for transport. Data from Fig. 2 indicates that NMP is also capable of im-proving the partitioning of hydrophilic drugs to the IPM

1. Embora cada sistema oferece um número ilimitado de formulações de amostra, que selecionado um representante W / O e O / W formulação de sistema de entrega transdérmica para 1 de teste de drogas hidrófilas e hidrófobas através da pele humana.Curiosamente, a permeabilidade da droga a partir de uma fase única homogénea composta de todos os componentes solúveis em água é semelhante ao fluxo de fármaco. Isto sugere que a fase oleosa na nossa formulação sirva como um depósito para a droga, enquanto que o transporte da droga ocorre principalmente a partir da fase da água. Este fenômeno poderia ter implicações significativas para o desenvolvimento de sistemas transdérmicos para a entrega sustentada de longo prazo.

1.  Para todas as drogas testadas, a Tabela V mostra que a constatação do fluxo é improvada em O / W em comparação com os sistemas de E / S W até mesmo para os fármacos hidrofóbicos sugere que o transporte seja da fase aquosa pois é fundamental. Quando a fase orgânica  foram removidos a partir do ME, deixando apenas os componentes da fase de água (H2O, etanol, NMP), o fluxo foi comparado com a do S / W-ME (Tabela IV). Trabalhos anteriores indicam que a sinergia H2O / NMP proporciona um maior aumento de fluxo de trans-dérmica de H2O / etanol. Embora a complexidade dos vários componentes do sistema faz com que seja difícil determinar as interacções moleculares exata,

3 -   Tem sido sugerido que a ME transdérmico é um resultado do aumento da concentração do fármaco na fase doadora . Nos nossos sistemas contendo o intensificador de NMP química, acreditamos que a permeabilidade efetiva da membrana é também afetada. O realce é apenas um efeito de concentração, então a permeabilidade da droga através da pele humana deve se manter constante. A permeabilidade de todas as quatro drogas foi a partir dos sistemas de mim contra o solvente (IPM ou H2O) em que eles foram mais solúveis (Tabela V) Há um aumento da permeabilidade claro para ambas as drogas hidrofílicas e hidrofóbicos dos sistemas ME. Este achado concorda com o trabalho anterior, onde descobrimos que NMP é capaz de melhorar a permeabilidade de drogas, tanto.