Development and in vitro evaluation of reservoir-type patch of coumarins in Angelicae Dahuricae Radix / 中草药

Objective To prepare the reservoir patch of coumarins in Angelicae Dahuricae Radix and investigate its release and transdermal absorption characteristics in vitro. The efficient enhancers were chosen to improve the drug’s permeation rate. Methods The reservoir patch was prepared using hydroxypropyl methylcellulose (HPMC) as medium and ethylene vinyl acetate (EVA) membrane to control the release of drug. The Franz diffusion cells were used and HPLC was used to determine imperatorin content and permeation rate. The content of imperatorin was determined by HPMC. The effect of the gel consumption, the content of coumarins and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model. The release of the selected patch in vitro was investigated. Results 1% HPMC, 1% coumarins in Angelicae Dahuricae Radix, 1% Isopropyl Myristate (IPM) and 3% Azone were the best permeation of the patch. The permeation rate reached 0.713 μg/(cm2•h). The release mechanisms of the patch in vitro coincided with zero-order kinetic. Conclusion The reservoir patch of coumarins in Angelicae Dahuricae Radix had high transdermal rate and complete in vitro release. It was indicated that the patch could be expected to be an effective transdermal drug delivery system.

Avaliação dos óleos essenciais de plantas nativas da Mata Atlântica como promotores de permeação cutânea / Evaluation of essential oils of plants native to the Atlantic Forest as skin permeation enhancers

Os óleos essenciais da Pimenta pseudocaryophyllus (Gomes) Landrum de planta de populações naturais de três ecossistemas, localizados na Ilha de Cananéia, região de restinga, no Morro da Cataia, cidade de Cajati, região de encosta, ambas em área de Mata Atlântica, e na Reserva Natural Morro Grande, cidade de Caldas, região de campos montanos, foram avaliados como promotores de permeação cutânea do diclofenaco de potássio. Os óleos essenciais foram extraídos de partes aéreas das plantas e o rendimento do processo foi entre 0,90% (p/p) e 2,7% (p/p). A análise da composição química mostrou diferenças, indicando tratar-se de três quimiotipos diferentes. A interação dos óleos essenciais e dos componentes majoritários com membrana biológica natural foi avaliada por FT-Raman e ATR- FTIR, indicando a interação com as porções lipídicas do tecido. Foram desenvolvidas seis membranas biológicas artificiais, compostas por ceramidas, ácidos graxos e colesterol em proporções equimolares, que foram caracterizadas por espectroscopia Raman confocal e foram consideradas semelhantes. As membranas foram utilizadas no desenvolvimento do sistema PAMPA (Parallel Artificial Membrane Permeability Assay) para avaliar a segurança e eficácia dos óleos essenciais e componentes majoritário como promotores de permeação do diclofenaco de potássio. Os resultados dos ensaios com o sistema PAMPA foram estatisticamente avaliados. A segurança foi avaliada com o critério de permeação mínima dos óleos através das membranas do sistema PAMPA, verificada pela absorbância mínima do eugenol na solução aceptora. Os óleos essenciais e componentes majoritários foram utilizados no pré-tratamento das membranas, nas concentrações de 0,125%, 0,25%, 0,50% e 2,00% (v/v) em etano!. Ensaios de permeação do diclofenaco de potássio no sistema PAMPA indicaram efeito de promoção da permeação para todos os compostos avaliados. O método de doseamento do fármaco por UV foi validado e utilizado para os ensaios de permeação de formulações de gel em base aquosa contendo o diclofenaco de potássio (1,0% p/p). As amostras de gel foram preparadas com o óleo procedente de Morro Grande, selecionado na etapa de avaliação de segurança, a 0,125% (p/v). Adicionalmente, foram preparadas formulações com citronelol e etanol, na mesma concentração. O óleo essencial da Reserva Natural Morro Grande teve efeito de promoção da permeação superior ao do citronelol e etanol, que foram equivalentes

The essential oils of the species Pimenta pseudocaryophyllus (Gomes) Landrum collected from natural populations of three existing ecosystems in the Cananéia Island, located at sea level, Cajati city, located in hillside region, both in the Atlantic Forest areas, as well as species collected in the Morro Grande Natural Reserve, region of montane fields, were evaluated as skin permeation enhancers of potassium diclofenac. Essential oils were extracted from the aerial parts of the plants and the process yield was between of 0.90% (w/w) and 2.7% (w/w). The chemical composition analysis showed differences between the plants of three origins, indicating that they are different chemotypes. The interaction of the essential oils and their major components with natural biological membrane was evaluated by FT- Raman and ATR-FTIR, indicating interaction with the Iipid portions of the natural membrane. Six artificial biological membranes have been developed, consisting of ceramides, cholesterol and fatty acids in equimolar proportions, which were characterized by confocal Raman spectroscopy and found to be similar. The membranes were used in developing the PAMPA (Parallel Artificial Membrane Permeability Assay) system to evaluate the safety of the potential permeation enhancers. The test results with PAMPA system were statistically evaluated. Safety was evaluated with the criterion of minimum permeation of the essential oil through the membranes, checked by the minimum absorbance of eugenol in the acceptor solution. The essential oils and the major components were used in the pretreatment of the membranes, at concentrations of 0.125%, 0.25%, 0.50% and 2.00% (v/v) in ethanol. Results indicated permeation enhancement effect for ali compounds evaluated. The analytical method for the quantification of potassium diclofenac was validated and used for the evaluation of the permeation of aqueous based gel formulations containing potassium diclofenac (1.0% w/w). The gel samples were prepared with the oil from Morro Grande Natural Reserve, selected in the safety evaluation step, at 0.125% (w/v). In addition, formulations were prepared with citronellol and ethanol at the same concentration. The essential Gil of Morro Grande Natural Reserve was more efficient as permeation enhancer than citronellol and ethanol under the test conditions

Formulation design, in vitro evaluation and stability studies on mucoadhesive buccal films of anti-anginal calcium channel blocker.

Diltiazem hydrochloride has poor oral bioavailability, easily undergo first passage effect in the liver. Hence, an attempt was made to prepare and evaluate mucoadhesive buccal films containing diltiazem hydrochloride by employing HPMC, eudragit, ethyl cellulose alone and in combination with PVP. The I.R and DSC studies showed that there was no interaction between drug and the utilized polymer. The prepared mucoadhesive buccal films showed uniform thickness, weight, folding endurance, surface pH, drug content and swelling index. The drug content of all the formulation was found to be uniform. In vitro drug release studies indicated that the films prepared with HPMC (3%) and ethyl cellulose (4%) has shown fast and slow release respectively. The formulations incorporated with SLS and sodium glycocholate indicated significant drug release from F11 and F15. Later the in-situ diffusion studies using goat cheek pouch showed faster drug release from film with 1% (SLS). About 93.04% and 91.83% of drug release profile were observed during in situ diffusion studies at the end of 9hrs and 18 hrs respectively. The formulated films were stable during stability studies at 45ºC and 75%RH with respect to drug content.

Study of Permeation Enhancers of Shuxiong Cataplasm / 中国中医药信息杂志

Objective To investigate the effect of two kinds of permeation enhancers,azone and clove bud oil,on transdermal permeation of Shuxiong cataplasm. Methods Cataplasm containing azone and clove bud oil,at different concentrations were prepared,with ferulic acid as the index,the role of enhancing permeation of azone and clove bud oil for the main active component were studied by in vitro permeation experiments. Results Both azone and clove bud oil at different concentrations could increase permeation. Clove bud oil was better than azone and the best concentration of Clove bud oil is 3%. Meanwhile,the permeation enhancing multiple of clove bud oil group was the highest which was 3.68. Conclusion With the cumulative permeation quantity of ferulic acid as the index,3% clove bud oil is more suitable to act as a permeation enhancer of Shuxiong cataplasm.

Permeability of integerrimine in vitro / 中草药

Object The permeability of integerrimine was studied in vitro to design its anticancer preparations Methods Vilia Chien diffusion cells were adopted as apparatus for in vitro skin permeation, nude mouse skins were used as permeation barrier and permeation coefficient (P) was calculated The concentrations of integerrimine in samples were measured by RP HPLC, and the effects of Azone, 4% Tween 80, 8% propylene glycol on it were studied Results Its P is 1 184?10 -2 cm/h with water solution as donor and pH 6 8 PBS as receptor Its enhancement rate (ER) of 2% Azone and 8% propylene glycol is 2 8 and 1 5, while Tween 80 inhibits its penetration Conclusion Integerrimine is a good candidate of antiskin cancer for transdermal drug delivery, and the optimal formulation can be designed according to the experiments