Screening of Ketoprofen-Poloxamer and Ketoprofen-Eudragit solid dispersions for improved physicochemical characteristics and dissolution profile

The aim of the present study was to enhance the dissolution rate of an NSAID drug Ketoprofen by formulating it into solid dispersions with water soluble carrier Poloxamer 188 and Eudragit S 100. The solid dispersions of Ketoprofen with Poloxamer 188 were prepared at 1:1, 1:1.5 and 1:2 (Ketoprofen: Poloxamer 188) ratio by Solvent evaporation methods. The same concentration ratio was used for the preparation of solid dispersion with Eudragit S 100 by melting/fusion technique. Further, solid dispersions were investigated by solubility, ATR-FTIR, XRD, DSC, surface morphology, in-vitro dissolution and accelerated stability study. Results demonstrated that both Poloxamer 188 and Eudragit S 100 improve solubility of drugs by 8­10 folds. The result of ATR-FTIR study showed the slight shifting/broadening of principle peaks. In vitro dissolution studies showed that in the solid dispersion system containing Ketoprofen: Poloxamer 188 batch P2 (1:1.5) gives faster dissolution rate of Ketoprofen than the physical mixtures. The solid dispersion with Eudragit S 100, batch E1 (1:1) gives faster dissolution rate of Ketoprofen than the physical mixtures. In phase solubility study with Poloxamer 188 showed concentration dependent solubilization of drug but Eudragit S 100 produced opposite result. The effect of pH on solubility of Eudragit S 100 was carried out which showed solubility at pH 7.4. The dissolution profile of solid dispersion with Eudragit S 100 at pH 7.4 gives excellent result. The Accelerated stability of solid dispersions & its physical mixtures were studied at 400±2 °C/75 ± 5% RH for a period of 1 month. In these studies, Solid Dispersion batches produced an unstable formulation. The Ketoprofen solid dispersions with Poloxamer 188 and Eudragit S 100 could be introduced as a suitable form with improved solubility

Formulation development and evaluation of colon targeted delayed release methotrexate pellets for the treatment of colonic carcinoma

Colonic carcinoma is one of the most common internal malignancies and is the second leading cause of deaths in United States. Methotrexate (MTX) is a drug of choice in the treatment of colon cancer. The aim of the present research work was to develop and characterize colon targeted pellets of MTX for treatment of colonic carcinoma. The product and process parameters were optimized by screening methods. Pellets were prepared by extrusion spheronization using microcrystalline cellulose (MCC) as spheronizing aid and ethyl cellulose (EC) as release retardant in different ratio. Based on the physical appearance, sphericity and % in vitro drug release, batch P17 containing EC: MCC (3:7) was optimized for core pellets. The site specificity was obtained by screening the coating polymers and by coating the core pellets with EudragitS100. The 32 full factorial design was applied in which airflow rate (X1) and coating time (X2) were the independent parameters and physical appearance (Y1) and time taken for 100% drug release (Y2) were selected as the dependent variables. From the results obtained, 6min of coating time and 60cm3/min airflow rate was optimized. The batch B5 showed appropriate physical appearance and % in vitro drug release upto 17hr indicating sustained release property. The ex-vivo studies performed on rat colon indicated a significant relation with the in vitro drug release. The drug release followed Higuchi's model indicating the diffusion pattern of drug release from the matrix of pellets. Thus, the coated pellets can be a good candidate for site specific delivery of MTX to colon by decreasing the gastric irritation and thus to improve bioavailability.

Microencapsulation of a Colombian Spodoptera frugiperda Nucleopolyhedrovirus with Eudragit® S100 by spray drying

A Colombian Spodoptera frugiperda nucleopolyhedrovirus NPV003 with high potential for the development of an efficient biopesticide was microencapsulated by spray drying with a pH dependent polymer (Eudragit® S100). Conditions for microparticles production were standardized and microencapsulation process was validated. Physical properties, insecticide activity and photo-stability of microencapsulated virus were determined. The microparticles were spherical and irregular shaped, with sizes between 17.64 and 19.47 µm. Moisture content was 10.38 ± 0.87%; encapsulation efficiency 84.61± 13.09% and process yield was 91.20 ± 6.40%. Microencapsulation process did not affect viral insecticidal activity and provided efficient protection against UVB radiation. Results demonstrated technological feasibility of spray drying process to be used in formulating a biopesticide based on NPV003.

In Vitro and In Vivo Evaluation of Combined Time and pH- Dependent Oral Colonic Targeted Prednisolone Microspheres.

Aims: to enhance the anti-inflammatory effect as well as oral absorption of prednisolone (PR), through formulation of colonic targeted microspheres prepared from a blend of time and pH- dependent polymers and loaded with PR. Study Design: In Vitro and In Vivo Evaluation of Combined Time and pH- Dependent Oral Colonic Targeted Prednisolone Microspheres. Place and Duration of Study: Department of Pharmaceutics and Industrial Pharmacy, Helwan University, Cairo, Egypt between June 2011 and October 2012. Methodology: Microspheres were prepared by solvent evaporation method using different ethyl cellulose (EC) and Eudragit® S-100 (ES100) ratios with 0.5 and 1% w/v span® 80 as emulsifier. The microspheres were evaluated for surface morphology, particle size, drug encapsulation efficiency % and in vitro drug release at pH 1.2 and 7.4. The antiinflammatory activity of selected formula was compared to that of conventional PR tablets. Results: A decrease in drug entrapment efficiency % was obtained with increasing both polymers and surfactant concentrations. Based on drug release results, the formula of 1: 1: 0.16 w/w/w, EC: ES100: PR ratio with 1% w/v span® 80 was selected for further histopathological evaluation of the anti-inflammatory activity in colitis induced-rats. Histopathological study showed undefined tissue necrosis after treatment with the selected microspheres; however, diffused necrosis was observed in rats treated with the commercial tablets. In vivo absorption study showed that values of Cmax and AUC0-24 of both formulations were insignificantly different. However, the occurrence of Cmax of microspheres was significantly delayed in comparison to free drug (9.17 to 2.67hr) (P<.001). Conclusion: This study has supplied us with brightening results concerning the therapeutic efficacy of a blend of time and pH- dependent polymers colonic targeted microspheres.

Multiparticulate formulation of Valdecoxib for the treatment of rheumatoid arthritis.

An oral controlled onset dosage form intended to approximate the chronobiology of rheumatoid arthritis was proposed for colonic targeting. The multiparticulate system comprising of non-pareil seeds coated with Eudragit S100 was designed for chronotherapeutic delivery of valdecoxib. The drug was coated onto non-pareil seeds by powder layering technique using the conventional coating pan. Different coat weights of non-aqueous dispersions were applied onto the drug-coated pellets using spray coating technique. In vitro dissolution tests of the coated pellets were performed in different pH media for a period of 11 hours. The in-vitro dissolution tests showed that the release of valdecoxib from the coated pellets depended on the pH of the dissolution fluid and the coat weights applied. All the formulations exhibited no release of drug in the pH 1.2 and pH 4 buffers; drug release took place in phosphate buffer of pH 7.4. Further intactness of the drug in the formulation and the uniformity of the polymer coating were checked by the infrared study and scanning electron microscopy. Stability studies inferred that the drug undergoes no considerable degradation pattern at room temperature and 40oC even after three weeks. All the above results show that the formulation could be highly advantageous in the chronotherapy of rheumatoid arthritis with appreciable drug release and physiochemical properties.

Development of Oral Colon Specific PH Dependent Microcapsules of NSAID Drug Naproxen.

The objective of present study is to develop oral colon specific pH dependant microcapsule of NSAID Drug Naproxen, to release drug in the colon and minimize or avoid local side effect by avoiding drug release in the upper git. Naproxen is encapsulated with Eudragit S 100 using O/W emulsion-solvent evaporation technique. Compatibility study was performed by I.R., D.S.C., X.R.D study. Microcapsules were evaluated for angle of repose, bulk density, tapped density, Carr’s index, particle size, drug loading, in-vitro drug release. The prepared microcapsules were white, free-flowing, and spherical in shape and particle size was in the range of 240.40-560.81μm. The drug-loaded microcapsules showed 69.88% to 98.73%. drug entrapment, angle of repose in the range of 28º.07” to 35 º.53”, bulk and tapped densities in the range of 0.4000 gm/cm3 to 0.4347 gm/cm3 and 0.4347gm/cm3 to 0.4787gm/cm3 respectively, Carr’s index ranges from 5.20 and 14.98. In vitro drug release studies were carried out up to 9th hr. in three different pH media, i.e., 0.1 N HCl (pH 1.2), phosphate buffer (pH 6.8 and 7.4). The drug-polymer concentration influences the particle size and drug release properties. All the formulations were following the Higuchi model of kinetic drug release.

Properties of polyacrylic resin Eudragit L100 and Eudragit S100 free film / 中国药学杂志

OBJECTIVE: To investigate the properties of polyacrylic: resin Eudragit L100-Eudragit S100 (mixed at ratio of 1:4) free film and its various influencing factors. METHODS: The free film was prepared by casting method,and its solubility parameter, intrinsic viscosity, tensile strength and permeability were determined. The optimal solvent and plaslicizer were screened. RESULTS: The tensile strength of the film prepared by ethanol was maximum, and the permeability of the free film made using acetone was the highest, therefore ethanol was the optimal solvent. Plasticizer could decrease the tensile strength and increase the permeability of free film,and diethyl phthalate was the optimal plasticizer. CONCLUSION: The present investigation might be helpful for screening coating formulation and optimizing coating process.

Extended release promethazine HCl using acrylic polymers by freeze-drying and spray-drying techniques: formulation considerations / Liberação prolongada prometazina HCl utilizando polímeros acrílicos por liofilização e técnicas de secagem por aspersão: consideração de formulação

The present study investigated a novel extended release system of promethazine hydrochloride (PHC) with acrylic polymers Eudragit RL100 and Eudragit S100 in different weight ratios (1:1 and 1: 5), and in combination (0.5+1.5), using freeze-drying and spray-drying techniques. Solid dispersions were characterized by Fourier-transformed infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), Powder X-ray diffractometry (PXRD), Nuclear magnetic resonance (NMR), Scanning electron microscopy (SEM), as well as solubility and in vitro dissolution studies in 0.1 N HCl (pH 1.2), double-distilled water and phosphate buffer (pH 7.4). Adsorption tests from drug solution to solid polymers were also performed. A selected solid dispersion system was developed into capsule dosage form and evaluated for in vitro dissolution studies. The progressive disappearance of drug peaks in thermotropic profiles of spray-dried dispersions were related to increasing amount of polymers, while SEM studies suggested homogenous dispersion of drug in polymer. Eudragit RL100 had a greater adsorptive capacity than Eudragit S100, and thus its combination in (0.5+1.5) for S100 and RL 100 exhibited a higher dissolution rate with 97.14 percent drug release for twelve hours. Among different formulations, capsules prepared by combination of acrylic polymers using spray-drying (1:0.5 + 1.5) displayed extended release of drug for twelve hours with 96.87 percent release followed by zero order kinetics (r²= 0.9986).

O presente trabalho compreendeu estudo de um novo sistema de liberação prolongada de cloridrato de prometazina (PHC) com polímeros acrílicos Eudragit RL100 e Eudragit S100 em diferentes proporções em massa (1:1 e 1:5) e em combinação (0,5+1,5), utilizando técnicas de liofilização e de secagem por aspersão As dispersões sólidas foram caracterizadas por espectrofotometria no infravermelho por transformada de Fourier (FT-IR), calorimetria diferencial de varredura (DSC), difratometria de raios X (PXRD), Ressonância Magnética Nuclear (RMN), microscopia eletrônica de varredura (SEM) e, também, por estudos de solubilidade e de dissolução in vitro em HCl 0,1 N (pH 1,2), água bidestilada e tampão fosfato (pH 7,4). Realizaram-se, também, testes de adsorção da solução do fármaco nos polímeros sólidos. Desenvolveu-se sistema de dispersão sólida exclusiva dentro das cápsulas, que foi avaliado por meio de estudos de dissolução in vitro. Relacionou-se o desaparecimento progressivo de picos do fármaco em perfis termotrópicos de dispersões secas por spray à quantidade aumentada de polímero, enquanto os estudos de SEM sugeriram dispersão homogênea do fármaco no polímero. O Eudragit RL100 apresentou maior capacidade de adsorção do que o Eudragit S100 e, dessa forma, a combinação de (0,5+1,5) para S100 e para RL100 mostrou taxa de dissolução maior, com liberação de 94,17 por cento de fármaco em 12 horas. Entre as várias formulações, as cápsulas preparadas pela combinação de polímeros acrílicos utilizando secagem por aspersão (0,5+1,5) apresentou liberação prolongada do fármaco em 12 horas, com 96,78 por cento de liberação, seguindo cinética de ordem zero (r² = 0,9986).

Assistance of Eudragit S-100 on protein refolding / 中国药科大学学报

Aim: To study the effect of Eudragit S-100, a pH-responsive polymer, on protein refolding level, using recombinant human keratinocyte growth factor-2 (rhKGF-2) as a model protein. Methods: The refolding of rh-KGF-2 was performed by directly diluting denatured rhKGF-2 into a refolding buffer containing different concentrations of Eudragit. The ability of Eudragit S-100 to enhance protein refolding level was investigated using MTT assay, reverse phase HPLC, fluorescence emission spectroscopy and circular dichroism spectroscopy. Results: The addition of Eudragit S-100 in the refolding buffer significantly increased the rhKGF-2 refolding yield to 71%, when dilution refolding was conducted at 0. 5 mg/mL rhKGF-2. The outcome from the refolding study showed possibility of a special interaction between rhKGF-2 and Eudragit, suggesting that the refolding-enhancing ability of Eudragit S-100 was due to this interaction between Eudragit S-100 and rhKGF-2. Mean while, the result showed that the concentration of urea was also an important factor for the optimization of the refolding in the presence of Eudragit. Conclusion: Eudragit S-100 can significantly increase the refolding level of rhKGF-2.

Estudio fisicoqíímico de la solubilidad del eudagit s100® en algunos medios accuosos y orgánicos / Physicochemicalsstudy of the solubility of eudragit s100® in some aqueous and organic systems / Esudo físico-quíímco da solubilidade de eudragit s100® em alguns sistemas aqueus e orânnicos

En este trabajo se estudió la solubilidad del Eudragit S100® respecto al pH en medios acuosos y a la polaridad en solventes orgánicos. Además, se estimó el parámetro de solubilidad del polímero [1], de forma experimental y teórica, mediante los métodos de contribución de grupos de Fedors y de van Krevelen, estableciendo su mapa de solubilidad. Los resultados mostraron que la solubilidad del polímero depende del pH siendo soluble a partir de pH 6,0. El valor [1] estimado experimentalmente fue de 12,9 [1] 2,4 cal1/2 cm-3/2 siendo casi concordante con los obtenidos mediante los métodos de Fedors y de van Krevelen. Adicionalmente, se construyó el diagrama de Teas para la identificación de solventes y no solventes para el polímero.

In this paper the solubility of Eudragit S100® was studied with respect to pH in aqueous media and with respect to the polarity of some organic solvents. The polymer solubility parameter [1], was established by means of experimental solubility determinations and by theoretical ways, by using the Fedors and van Krevelen methods, which are based on groups’ contribution. The respective solubility map was thus established. The results show that the polymer is soluble in water over pH 6.0. The [1] value obtained experimentally was 12.9 [1] 2.4 cal1/2 cm-3/2, which is almost concordant with those obtained by means of Fedors and van Krevelen’s methods. In turn, the Teas diagram was developed for identifying the solvents and non-solvents for this polymer.

Neste papel o solubilidade de Eudragit S100® foi estudado com respeito ao pH em meios aqueus e com respeito à polaridade de alguns solventes orgânicos. O parâmetro da solubilidade ( ) do polímero foi estabelecido por meio das determinações experimentais da solubilidade e por maneiras teóricas, usando os métodos de Fedors e de van Krevelen, que são baseados na contribuição dos grupos funcionais. O mapa respectivo da solubilidade foi estabelecido assim. Os resultados mostram que o polímero é solúvel na água a pH maior que 6,0. O valor obtido experimentalmente foram 12,9 [1] 2,4 cal1/2 cm-3/2, que é quase concordante com os aqueles obtidos por meio de métodos de Fedors e de van Krevelen. Por sua vez, o diagrama dos Teas foi desenvolvido identificando os solventes e os não solventes para este polímero.