Silymarin-Laden PVP-Nanocontainers Prepared Via the Electrospraying Technique for Improved Aqueous Solubility and Dissolution Rate

Abstract The aim of the present research was to develop a silymarin-laden PVP-nanocontainer providing ameliorated aqueous solubility and dissolution of the drug. Several silymarin-laden formulations were formed with varying quantities of PVP and SDS via the solvent evaporation method using the electrospraying technique. The influence of the hydrophilic carriers on solubility and dissolution was explored. The solid-state characterization was carried out by particle-size analysis, PXRD, DSC, FTIR and SEM. All of the formulations demonstrated better solubility and dissolution than did silymarin plain powder. Both the SDS and PVP had positive effects on solubility and dissolution of silymarin in the aqueous media. An increased solubility was attained as the drug/PVP ratio was 1/4; however, further increase in PVP did not provide significant improvement. In particular, a nanocontainer formulation prepared with silymarin, PVP and SDS (1/4/0.5, w/w/w) exhibited the best solubility (26432.76 ± 1749.00 μg/mL) and an excellent dissolution (~92 % in 20 min) than did silymarin plain powder. Also, it demonstrated similar dissolution profiles compared to a commercial product; therefore, might be bioequivalent to the commercial product (f 1 = 3 and f 2 = 69). Moreover, cumulative undersize distribution values as represented by X10, X50 and X90 were 201 ± 21.01 nm, 488 ± 36.05 nm and 392 ± 48.10 nm, respectively. The drug existed in the amorphous state in the PVP-nanocontainers with no strong chemical bonding with other excipients. Thus, this formulation might be used for more effective administration of silymarin via the oral route.

Silymarin-laden PVP-PEG polymeric composite for enhanced aqueous solubility and dissolution rate: Preparation and in vitro characterization / 药物分析学报

The aim of this work was to develop, optimize and characterize a silymarin-laden polyvinylpyrrolidone (PVP)-polyethylene glycol (PEG) polymeric composite to resolve low aqueous solubility and dissolution rate problem of the drug. A number of silymarin-laden polymeric formulations were fabricated with different quantities of PVP K-30 and PEG 6000 by the solvent-evaporation method. The effect of PVP K-30 and PEG 6000 on the aqueous solubility and dissolution rate was investigated. The optimized formula-tion and its constituents were characterized using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) techniques. Both the PEG 6000 and PVP K-30 positively affected the aqueous solubility and dis-solution rate of the drug. In particular, a formulation consisting of silymarin, PVP K-30 and PEG 6000 (0.25/1.5/1.5, w/w/w) furnished the highest solubility (24.3972.95 mg/mL) and an excellent dissolution profile (～100％ in 40 min). The solubility enhancement with this formulation was ～1150-fold as com-pared to plain silymarin powder. Moreover, all the constituents existed in the amorphous state in this silymarin-laden PVP-PEG polymeric composite. Accordingly, this formulation might be a promising tool to administer silymarin with an enhanced effect via the oral route.

pH-sensitive polyvinylpyrrolidone-acrylic acid hydrogels: Impact of material parameters on swelling and drug release

In this study, we fabricated pH-sensitive polyvinylpyrrolidone/acrylic acid (PVP/AA) hydrogels by a free-radical polymerisation method with variation in the content of monomer, polymer and cross-linking agent. Swelling was performed in USP phosphate buffer solutions of pH 1.2, 5.5, 6.5 and 7.5 with constant ionic strength. Network structure was evaluated by different parameters and FTIR confirmed the formation of cross-linked hydrogels. X-ray crystallography showed molecular dispersion of tramadol HCl. A drug release study was carried out in phosphate buffer solutions of pH 1.2, 5.5 and 7.5 for selected samples. It was observed that swelling and drug release from hydrogels can be modified by changing composition and degree of cross-linking of the hydrogels under investigation. Swelling coefficient was high at higher pH values except for the one containing high PVP content. Drug release increased by increasing the pH of the medium and AA contents in hydrogels while increasing the concentration of cross-linking agent had the opposite effect. Analysis of the drug release mechanism revealed non-Fickian transport of tramadol from the hydrogels.

Nesse estudo, preparamos hidrogéis de polivinilpirrolidona/ácido acrílico(PVP/AA), sensíveis ao pH, por meio de método de polimerização de radical livre, com variações no conteúdo de monômero, de polímero e de agente de ligação cruzada. O inchamento foi realizado em soluções tampão fosfato USP pH 1,2, 5,5, 6,5 e 7,5, com força iônica constante. A estrutura reticular foi avaliada por diferentes parâmetros e o FTIR confirmou a formação de hidrogéis de ligação cruzada. A cristalografia de raios X mostrou dispersão molecular do cloridrato de tramadol. Realizou-se estudo de liberação do fármaco em soluções tampão fosfato pH 1,2, 5,5 e 7,5 para amostras selecionadas. Observou-se que o inchamento e a liberação do fármaco dos hidrogéis podem ser modificados mudando-se a composição e o grau de ligação cruzada dos hidrogéis em estudo. O coeficiente de inchamento foi alto em pH mais altos, exceto para um deles com alto conteúdo de PVP. A liberação do fármaco aumentou com o aumento do pH do meio e do conteúdo em AA nos hidrogéis, enquanto que o aumento na concentração do agente de ligação cruzada apresentou efeito oposto. A análise do mecanismo de liberação do fármaco revelou transporte não Fickiano do tramadol dos hidrogéis.

The evaluation of coated granules to mask the bitter taste of dihydroartemisinin / A avaliação de grânulos revestidos para mascarar o sabor amargo da diidroartemisina

The purpose of this study was to mask the bitter taste imparted by dihydroartemisinin (DHA) by the use of different coating materials. Trial-1 and trial-2 were conducted to prepare the DHA granules. The granules produced from trial-1 were irregular in shape and smaller in size while the trial-2 granules were more regular and larger in size. The granules obtained from both trials were then coated with two different coating methods, namely A and B, depending upon coating material. The trial-2 granules showed better flow properties than trial-1 granules. In vitro dissolution studies in phosphate buffer at pH 6.8 revealed that granules of trial-2B released only 34 percent ± 3 DHA in two minutes compared with trial-1A (57 percent ± 2), trial-1B (48 percent ± 2) and trial-2A (53 percent ± 7). The pleasant taste perception (PTP) test also confirmed the taste masking efficacy of trial-2B (P < 0.05). Scanning electron microscopy (SEM) revealed the more regular and smooth surface of trial-2B granules. In addition, the differential thermal and thermogravimetric analysis (TG-DTA) confirmed no interaction between the materials and pure DHA. DHA has shown its characteristic peaks in the x-ray diffraction (XRD) patterns which were also prominent in all the granules. In conclusion, the granules obtained from trial-2B displayed considerable decrease in the bitter taste of DHA thereby fulfilling the purpose of this study.

O objetivo deste estudo foi o de mascarar o gosto amargo característico da diidroartemisinina (DHA) pelo uso de diferentes materiais de revestimento. Experimento-1 e experimento-2 foram realizados para preparar grânulos de DHA. Os grânulos produzidos pelo experimento-1 mostraram-se irregulares e menores se comparados aos obtidos pelo experimento-2, que foram mais regulares e maiores. Os grânulos obtidos em ambos os experimentos foram, então, revestidos por dois métodos distintos de revestimento, designados como A e B, dependendo do material de revestimento empregado. Os grânulos do experimento-2 mostraram melhor propriedade de fluxo que os obtidos no experimento-1. Estudos de dissolução in vitro em tampão fosfato pH 6,8 revelaram que grânulos do experimento-2B liberaram apenas 34 por cento ± 3 da DHA em dois minutos se comparado com experimento-1A (57 por cento ± 2), experimento-1B (48 por cento ± 2) e experimento-2A (53 por cento ± 7). A Análise Sensorial quanto ao sabor (Pleasant Taste Perception - PTP) também confirmou a eficácia do experimento-2B (P <0,05) em mascarar o gosto amargo da DHA. Microscopia Eletrônica de Varredura (SEM) revelou a superfície mais regular e lisa dos grânulos obtidos pelo experimento-2B. Além disso, Análise Termogravimétrica e Análise Térmica Diferencial (TG-DTA) confirmaram que não há nenhuma interação entre os materiais e a DHA pura. DHA mostrou seus picos característicos na Difração de Raios X (XRD) em padrões que também foram proeminentes em todas as amostras. Em conclusão, os grânulos obtidos pelo experimento-2B exibiram diminuição considerável no gosto amargo da DHA, o que era o propósito deste estudo.