Cápsulas resistentes ao trato gastrintestinal são freqüentemente usadas com diversos propósitos. Estas cápsulas promovem eficácia farmacológica e farmacocinética de substâncias que são instáveis, ou irritantes para a mucosa gástrica. O diclofenaco de sódio é um antiinflamatório não-esteróide, que, por ser muito utilizado, despertou o interesse do setor magistral para sua manipulação. Porém, o fármaco é irritante para a mucosa gástrica, havendo necessidade de se empregar substâncias capazes de proteger o meio gástrico da ação do medicamento e uma alternativa para o setor magistral é a manipulação de cápsulas gastro-resistentes. Estas cápsulas devem resistir, sem alteração, à ação do suco gástrico, mas desagregar-se rapidamente no suco intestinal. O objetivo deste trabalho foi preparar cápsulas na concentração de 50 mg/cápsula de diclofenaco de sódio formiladas ou revestidas com acetoftalato de celulose ou com Eudragit L100 na máquina de revestimento entérico “Enteric Coating Machine” PCCA ou manualmente. Foram analisados os resultados considerando o perfil de dissolução das formulações. Observou-se que as cápsulas revestidas na máquina com Eudragit L100 e com acetoftalato em acetona revestidas na máquina e manualmente mostraram bons resultados quanto à dissolução, porém, não apresentaram boa aparência no caso das cápsulas de cor vermelha. Quanto às cápsulas revestidas com formol, estas apresentam boa aparência, mas não deram bons resultados no teste de dissolução.

Cápsulas resistentes ao trato gastrintestinal são freqüentemente usadas com diversos propósitos. Estas cápsulas promovem eficácia farmacológica e farmacocinética de substâncias que são instáveis, ou irritantes para a mucosa gástrica. O diclofenaco de sódio é um antiinflamatório não-esteróide, que, por ser muito utilizado, despertou o interesse do setor magistral para sua manipulação. Porém, o fármaco é irritante para a mucosa gástrica, havendo necessidade de se empregar substâncias capazes de proteger o meio gástrico da ação do medicamento e uma alternativa para o setor magistral é a manipulação de cápsulas gastro-resistentes. Estas cápsulas devem resistir, sem alteração, à ação do suco gástrico, mas desagregar-se rapidamente no suco intestinal. O objetivo deste trabalho foi preparar cápsulas na concentração de 50 mg/cápsula de diclofenaco de sódio formiladas ou revestidas com acetoftalato de celulose ou com Eudragit L100 na máquina de revestimento entérico “Enteric Coating Machine” PCCA ou manualmente. Foram analisados os resultados considerando o perfil de dissolução das formulações. Observou-se que as cápsulas revestidas na máquina com Eudragit L100 e com acetoftalato em acetona revestidas na máquina e manualmente mostraram bons resultados quanto à dissolução, porém, não apresentaram boa aparência no caso das cápsulas de cor vermelha. Quanto às cápsulas revestidas com formol, estas apresentam boa aparência, mas não deram bons resultados no teste de dissolução.

Cápsulas resistentes ao trato gastrintestinal são freqüentemente usadas com diversos propósitos. Estas cápsulas promovem eficácia farmacológica e farmacocinética de substâncias que são instáveis, ou irritantes para a mucosa gástrica. O diclofenaco de sódio é um antiinflamatório não-esteróide, que, por ser muito utilizado, despertou o interesse do setor magistral para sua manipulação. Porém, o fármaco é irritante para a mucosa gástrica, havendo necessidade de se empregar substâncias capazes de proteger o meio gástrico da ação do medicamento e uma alternativa para o setor magistral é a manipulação de cápsulas gastro-resistentes. Estas cápsulas devem resistir, sem alteração, à ação do suco gástrico, mas desagregar-se rapidamente no suco intestinal. O objetivo deste trabalho foi preparar cápsulas na concentração de 50 mg/cápsula de diclofenaco de sódio formiladas ou revestidas com acetoftalato de celulose ou com Eudragit L100 na máquina de revestimento entérico “Enteric Coating Machine” PCCA ou manualmente. Foram analisados os resultados considerando o perfil de dissolução das formulações. Observou-se que as cápsulas revestidas na máquina com Eudragit L100 e com acetoftalato em acetona revestidas na máquina e manualmente mostraram bons resultados quanto à dissolução, porém, não apresentaram boa aparência no caso das cápsulas de cor vermelha. Quanto às cápsulas revestidas com formol, estas apresentam boa aparência, mas não deram bons resultados no teste de dissolução.

The purpose of this research project was to develop and characterise matrix type microspheres prepared from Eudragit® L100, containing insulin as model peptide drug as well as an absorption enhancer, N-trimethyl chitosan chloride (TMC), to improve intestinal absorption via the paracellular route. Insulin loaded microspheres were prepared using a single water in oil emulsification/evaporation method in accordance with a fractional factorial design (23) and subsequently characterised in terms of morphology as well as internal structure. Also, insulin and TMC loading were determined using a high pressure liquid chromatography analysis (HPLC) and colorimetric assay, respectively. Scanning electron microscopic characterisation revealed that most microsphere formulations showed a spherical shape and smooth surface with a sponge-like internal structure as well as relatively good homogeneity in terms of size distribution. Insulin loading ranged from 27.9 ± 14.25 – 52.4 ± 2.72% between the different formulations. TMC loading was lower than for insulin and ranged from 29.1 ± 3.3 - 37.7 ± 2.3% between the different formulations. The pronounced difference in insulin and TMC loading between the microsphere formulations is probably the result of the multitude parameters involved as well as the complex physicochemical processes which govern emulsification/solvent evaporation. Based on the microsphere characterisation results, two formulations were selected (i.e. B and F) for further characterisation (i.e. particle size distribution, dissolution behaviour, and enteric nature) and for in vitro evaluation of insulin transport across excised Fischer (FSR) rat intestinal tissue using a Sweetana-Grass diffusion chamber. Particle size analysis by means of laser light diffraction of the two selected microsphere formulations revealed that the mean particle size (based on volume) ranged from 135.7 ± 41.05 to 157.3 ± 31.74 m. Dissolution results for microsphere Formulations B and F revealed that both insulin and TMC were released from the microsphere formulations in an alkaline environment (pH 7.4). The mean dissolution time (MDT) for insulin ranged from 34.5 ± 4.01 to 42.6 ± 9.06 min, while the MDT for TMC ranged from 1.2 ± 1.73 to 6.8 ± 6.42 min. Statistical analysis revealed no significant differences in the MDT of either insulin or TMC (p-value > 0.05) between the two formulations, although the difference between insulin and TMC of each formulation was significant (p-value < 0.05). Microsphere formulations B and F released 36.92 and 48.21% of their total drug content over a period of 1 h in 0.1 M HCl. Microsphere Formulation B showed 8.3 ± 0.52% and formulation F 8.9 ± 2.26% transport of the initial insulin dose after a period of 120 min across excised rat intestinal tissue. The increase in insulin transport by the microsphere formulations compared to that of the control group (i.e. insulin alone) correlated well with the decrease in transepithelial electrical resistance (TEER) caused by the microsphere formulations. The transport of insulin from Formulations B and F represented transport enhancement ratios of 10.67 and 9.68, respectively. Insulin loaded EudragitL100 microspheres containing TMC were successfully prepared by emulsification/solvent evaporation that demonstrated promising potential to serve as oral drug delivery systems for insulin. The microspheres exhibited improved insulin permeability across intestinal epithelial tissue; however, its enteric properties should be improved and clinical effectiveness need to be confirmed by future in vivo studies. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

The purpose of this research project was to develop and characterise matrix type microspheres prepared from Eudragit® L100, containing insulin as model peptide drug as well as an absorption enhancer, N-trimethyl chitosan chloride (TMC), to improve intestinal absorption via the paracellular route. Insulin loaded microspheres were prepared using a single water in oil emulsification/evaporation method in accordance with a fractional factorial design (23) and subsequently characterised in terms of morphology as well as internal structure. Also, insulin and TMC loading were determined using a high pressure liquid chromatography analysis (HPLC) and colorimetric assay, respectively. Scanning electron microscopic characterisation revealed that most microsphere formulations showed a spherical shape and smooth surface with a sponge-like internal structure as well as relatively good homogeneity in terms of size distribution. Insulin loading ranged from 27.9 ± 14.25 – 52.4 ± 2.72% between the different formulations. TMC loading was lower than for insulin and ranged from 29.1 ± 3.3 - 37.7 ± 2.3% between the different formulations. The pronounced difference in insulin and TMC loading between the microsphere formulations is probably the result of the multitude parameters involved as well as the complex physicochemical processes which govern emulsification/solvent evaporation. Based on the microsphere characterisation results, two formulations were selected (i.e. B and F) for further characterisation (i.e. particle size distribution, dissolution behaviour, and enteric nature) and for in vitro evaluation of insulin transport across excised Fischer (FSR) rat intestinal tissue using a Sweetana-Grass diffusion chamber. Particle size analysis by means of laser light diffraction of the two selected microsphere formulations revealed that the mean particle size (based on volume) ranged from 135.7 ± 41.05 to 157.3 ± 31.74 m. Dissolution results for microsphere Formulations B and F revealed that both insulin and TMC were released from the microsphere formulations in an alkaline environment (pH 7.4). The mean dissolution time (MDT) for insulin ranged from 34.5 ± 4.01 to 42.6 ± 9.06 min, while the MDT for TMC ranged from 1.2 ± 1.73 to 6.8 ± 6.42 min. Statistical analysis revealed no significant differences in the MDT of either insulin or TMC (p-value > 0.05) between the two formulations, although the difference between insulin and TMC of each formulation was significant (p-value < 0.05). Microsphere formulations B and F released 36.92 and 48.21% of their total drug content over a period of 1 h in 0.1 M HCl. Microsphere Formulation B showed 8.3 ± 0.52% and formulation F 8.9 ± 2.26% transport of the initial insulin dose after a period of 120 min across excised rat intestinal tissue. The increase in insulin transport by the microsphere formulations compared to that of the control group (i.e. insulin alone) correlated well with the decrease in transepithelial electrical resistance (TEER) caused by the microsphere formulations. The transport of insulin from Formulations B and F represented transport enhancement ratios of 10.67 and 9.68, respectively. Insulin loaded EudragitL100 microspheres containing TMC were successfully prepared by emulsification/solvent evaporation that demonstrated promising potential to serve as oral drug delivery systems for insulin. The microspheres exhibited improved insulin permeability across intestinal epithelial tissue; however, its enteric properties should be improved and clinical effectiveness need to be confirmed by future in vivo studies. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.