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Design, Development, and Optimization of Sterculia Gum-Based Tablet Coated with Chitosan/Eudragit RLPO Mixed Blend Polymers for Possible Colonic Drug Delivery.

Nath B, Nath LK - J Pharm (Cairo) (2012)

Bottom Line: Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon.Release kinetic data revealed that the optimized MCDDS was fitted well into first-order model, and apparent lag time was found to be 6 hours, followed by Higuchi release kinetics.In vivo study in rabbits shows delayed T max, prolonged absorption time, decreased C max, and absorption rate constant (Ka), indicating a reduced systemic toxicity of the drug as compared to other dosage forms.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Girijananda Chowdhury Institute of Pharmaceutical Sciences (GIPS), Azara, Assam, Guwahati 781001, India ; Girijananda Chowdhury Institute of Pharmaceutical Sciences (GIPS) Affiliated to Gauhati University, Azara, Assam, Guwahati 781017, India.

ABSTRACT
The purpose of this study is to explore the possible applicability of Sterculia urens gum as a novel carrier for colonic delivery system of a sparingly soluble drug, azathioprine. The study involves designing a microflora triggered colon-targeted drug delivery system (MCDDS) which consists of a central polysaccharide core and is coated to different film thicknesses with blends of chitosan/Eudragit RLPO, and is overcoated with Eudragit L00 to provide acid and intestinal resistance. The microflora degradation property of gum was investigated in rat caecal medium. Drug release study in simulated colonic fluid revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that the optimized MCDDS was fitted well into first-order model, and apparent lag time was found to be 6 hours, followed by Higuchi release kinetics. In vivo study in rabbits shows delayed T max, prolonged absorption time, decreased C max, and absorption rate constant (Ka), indicating a reduced systemic toxicity of the drug as compared to other dosage forms.

No MeSH data available.


Related in: MedlinePlus

Comparison of mean plasma drug concentration versus time profile curve after oral administration of MKT tablet (–), EC tablet (▵) and MCDDS (–) of AZA in rabbit.
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fig7: Comparison of mean plasma drug concentration versus time profile curve after oral administration of MKT tablet (–), EC tablet (▵) and MCDDS (–) of AZA in rabbit.

Mentions: Mean plasma 6-MP concentration versus time profiles after a single oral dose of MKT, EC, and MCDDS are depicted in Figure 7. Mean values of pharmacokinetic parameters are summarized in Table 5. In case of, MKT, the peak plasma concentration (Cmax) of 6-MP was obtained within 1.5 h of administration, indicating the immediate absorption of AZA from the gastrointestinal tract and quick conversion into its active metabolite, 6-MP in blood. The Cmax value of 6-MP following oral administration of MKT tablet was found to be 1430.08 ng/mL at the time maximum (Tmax) of 1.5 h. The Cmax value of 6-MP for EC tablet of AZA without containing sterculia gum was found to be 847.5 ng/mL at Tmax of 5.0 h. From the results of in vitro release study, it was observed that the drug was released after 2.0 h of dissolution study which was quite desirable, due to the fact that the drug would be released from the tablets after passing the stomach region as the tablets were enteric coated. The results of in vivo studies of EC tablets showed that drug was not released in the stomach up to 2.0 h and therefore it gives Tmax of 5.0 h. Thus, the in vivo finding has good correlation with the in vitro results. A lag time of 6.0 h was observed from the MCDDS which revealed that the tablet had passed through the GIT and after reaching the colon only the drug was released and appeared in plasma as 6-MP. Therefore, the Cmax value of 6-MP for the MCDDS could found to be 453.56 ng/mL at Tmax of 9.0 h after oral administration. The results of ANOVA revealed that there was significant difference of AUC0-∞ between the MCDDS, EC and MKT formulation (P < 0.05). The results explained that the MKT formulation was more rapidly absorbed from the upper gastrointestinal tract of rabbit. But the EC and MCDDS were not absorbed from the upper GIT due to which they showed greater value of AUC0−∞ as shown in the Table 5. It is evident that AUC for MCDDS was higher as compared to the reference formulation EC and MKT formulations (MCDDS < EC < MKT). Result suggests that the extent of absorption of AZA from the developed MCDDS was decreased from the large intestine, but increased from the upper part of the GIT as seen in case of EC and MKT formulation. From the in vivo studies, the Cmax of MCDDS was found to be almost half of the EC tablet without containing sterculia gum. The longer Tmax value (9.0 h) and low Cmax value (453.56 ng/mL) of MCDDS as compared to the reference formulations had proved that the MCDDS released drug only at the colonic region of the rabbit intestine. This reveals localization of the drug in the colonic mucosa from the MCDDS and thereby, possibly reducing the risk of systemic toxicity.


Design, Development, and Optimization of Sterculia Gum-Based Tablet Coated with Chitosan/Eudragit RLPO Mixed Blend Polymers for Possible Colonic Drug Delivery.

Nath B, Nath LK - J Pharm (Cairo) (2012)

Comparison of mean plasma drug concentration versus time profile curve after oral administration of MKT tablet (–), EC tablet (▵) and MCDDS (–) of AZA in rabbit.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4595939&req=5

fig7: Comparison of mean plasma drug concentration versus time profile curve after oral administration of MKT tablet (–), EC tablet (▵) and MCDDS (–) of AZA in rabbit.
Mentions: Mean plasma 6-MP concentration versus time profiles after a single oral dose of MKT, EC, and MCDDS are depicted in Figure 7. Mean values of pharmacokinetic parameters are summarized in Table 5. In case of, MKT, the peak plasma concentration (Cmax) of 6-MP was obtained within 1.5 h of administration, indicating the immediate absorption of AZA from the gastrointestinal tract and quick conversion into its active metabolite, 6-MP in blood. The Cmax value of 6-MP following oral administration of MKT tablet was found to be 1430.08 ng/mL at the time maximum (Tmax) of 1.5 h. The Cmax value of 6-MP for EC tablet of AZA without containing sterculia gum was found to be 847.5 ng/mL at Tmax of 5.0 h. From the results of in vitro release study, it was observed that the drug was released after 2.0 h of dissolution study which was quite desirable, due to the fact that the drug would be released from the tablets after passing the stomach region as the tablets were enteric coated. The results of in vivo studies of EC tablets showed that drug was not released in the stomach up to 2.0 h and therefore it gives Tmax of 5.0 h. Thus, the in vivo finding has good correlation with the in vitro results. A lag time of 6.0 h was observed from the MCDDS which revealed that the tablet had passed through the GIT and after reaching the colon only the drug was released and appeared in plasma as 6-MP. Therefore, the Cmax value of 6-MP for the MCDDS could found to be 453.56 ng/mL at Tmax of 9.0 h after oral administration. The results of ANOVA revealed that there was significant difference of AUC0-∞ between the MCDDS, EC and MKT formulation (P < 0.05). The results explained that the MKT formulation was more rapidly absorbed from the upper gastrointestinal tract of rabbit. But the EC and MCDDS were not absorbed from the upper GIT due to which they showed greater value of AUC0−∞ as shown in the Table 5. It is evident that AUC for MCDDS was higher as compared to the reference formulation EC and MKT formulations (MCDDS < EC < MKT). Result suggests that the extent of absorption of AZA from the developed MCDDS was decreased from the large intestine, but increased from the upper part of the GIT as seen in case of EC and MKT formulation. From the in vivo studies, the Cmax of MCDDS was found to be almost half of the EC tablet without containing sterculia gum. The longer Tmax value (9.0 h) and low Cmax value (453.56 ng/mL) of MCDDS as compared to the reference formulations had proved that the MCDDS released drug only at the colonic region of the rabbit intestine. This reveals localization of the drug in the colonic mucosa from the MCDDS and thereby, possibly reducing the risk of systemic toxicity.

Bottom Line: Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon.Release kinetic data revealed that the optimized MCDDS was fitted well into first-order model, and apparent lag time was found to be 6 hours, followed by Higuchi release kinetics.In vivo study in rabbits shows delayed T max, prolonged absorption time, decreased C max, and absorption rate constant (Ka), indicating a reduced systemic toxicity of the drug as compared to other dosage forms.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Girijananda Chowdhury Institute of Pharmaceutical Sciences (GIPS), Azara, Assam, Guwahati 781001, India ; Girijananda Chowdhury Institute of Pharmaceutical Sciences (GIPS) Affiliated to Gauhati University, Azara, Assam, Guwahati 781017, India.

ABSTRACT
The purpose of this study is to explore the possible applicability of Sterculia urens gum as a novel carrier for colonic delivery system of a sparingly soluble drug, azathioprine. The study involves designing a microflora triggered colon-targeted drug delivery system (MCDDS) which consists of a central polysaccharide core and is coated to different film thicknesses with blends of chitosan/Eudragit RLPO, and is overcoated with Eudragit L00 to provide acid and intestinal resistance. The microflora degradation property of gum was investigated in rat caecal medium. Drug release study in simulated colonic fluid revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that the optimized MCDDS was fitted well into first-order model, and apparent lag time was found to be 6 hours, followed by Higuchi release kinetics. In vivo study in rabbits shows delayed T max, prolonged absorption time, decreased C max, and absorption rate constant (Ka), indicating a reduced systemic toxicity of the drug as compared to other dosage forms.

No MeSH data available.


Related in: MedlinePlus