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Gellan gum-based mucoadhesive microspheres of almotriptan for nasal administration: Formulation optimization using factorial design, characterization, and in vitro evaluation.

Abbas Z, Marihal S - J Pharm Bioallied Sci (2014)

Bottom Line: Regression analysis was performed to identify the best formulation conditions.In vitro drug diffusion was Higuchi matrix controlled and the release mechanism was found to be non-Fickian.Stability studies indicated that there were no significant deviations in the drug content, in vitro mucoadhesion and in vitro drug diffusion characteristics.

View Article: PubMed Central - PubMed

Affiliation: Research Scientist, Formulation Development Department, Apotex Research Private Limited, Bangalore - 560 099, India.

ABSTRACT

Background: Almotriptan malate (ALM), indicated for the treatment of migraine in adults is not a drug candidate feasible to be administered through the oral route during the attack due to its associated symptoms such as nausea and vomiting. This obviates an alternative dosage form and nasal drug delivery is a good substitute to oral and parenteral administration.

Materials and methods: Gellan gum (GG) microspheres of ALM, for intranasal administration were prepared by water-in-oil emulsification cross-linking technique employing a 2(3) factorial design. Drug to polymer ratio, calcium chloride concentration and cross-linking time were selected as independent variables, while particle size and in vitro mucoadhesion of the microspheres were investigated as dependent variables. Regression analysis was performed to identify the best formulation conditions. The microspheres were evaluated for characteristics such as practical percentage yield, particle size, percentage incorporation efficiency, swellability, zeta potential, in vitro mucoadhesion, thermal analysis, X-ray diffraction study, and in vitro drug diffusion studies.

Results: The shape and surface characteristics of the microspheres were determined by scanning electron microscopy, which revealed spherical nature and nearly smooth surface with drug incorporation efficiency in the range of 71.65 ± 1.09% - 91.65 ± 1.13%. In vitro mucoadhesion was observed the range of 79.45 ± 1.69% - 95.48 ± 1.27%. Differential scanning calorimetry and X-ray diffraction results indicated a molecular level dispersion of drug in the microspheres. In vitro drug diffusion was Higuchi matrix controlled and the release mechanism was found to be non-Fickian. Stability studies indicated that there were no significant deviations in the drug content, in vitro mucoadhesion and in vitro drug diffusion characteristics.

Conclusion: The investigation revealed promising potential of GG microspheres for delivering ALM intranasally for the treatment of migraine.

No MeSH data available.


Related in: MedlinePlus

In vitro drug diffusion profile of microsphere formulation AGM1 to AGM4 (a) and AGM5 to AGM8 (b)
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Figure 5: In vitro drug diffusion profile of microsphere formulation AGM1 to AGM4 (a) and AGM5 to AGM8 (b)

Mentions: The in vitro diffusion of ALM from the prepared microspheres exhibited a biphasic mechanism. The release of ALM from the microspheres was characterized by an initial phase of burst effect due to the presence of drug particles on the surface of the microspheres followed by a second phase of moderate release. The initial burst effect is a desired effect to achieve initial therapeutic plasma concentration of the drug. The in vitro drug diffusion study from formulations AGM1 to AGM4 is presented in Figure 5a. As the concentration of CaCl2 and cross-linking time increased, percentage drug dissolved decreased. The in vitro drug diffusion study from formulations AGM5 to AGM8 are presented in Figure 5b. The decrease in percentage drug dissolved could be attributed to increase in the extent of cross-linking in the microsphere with an increase in the amount of cross-linking agent. The Ca2+ cross-linked microspheres form three-dimensional bonding structures with the GG inside the microspheres. This three-dimensional bonding results in extended cross-linking through the whole microsphere producing hard microcapsules with lower water uptake and thus leading to slow removal of drug in the dissolution media. The release of the drug has been controlled by swelling control release mechanism. In addition, the larger particle size at higher polymer concentration also restricts the total surface area thus resulting in slower drug release over a span of 8 h.


Gellan gum-based mucoadhesive microspheres of almotriptan for nasal administration: Formulation optimization using factorial design, characterization, and in vitro evaluation.

Abbas Z, Marihal S - J Pharm Bioallied Sci (2014)

In vitro drug diffusion profile of microsphere formulation AGM1 to AGM4 (a) and AGM5 to AGM8 (b)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231387&req=5

Figure 5: In vitro drug diffusion profile of microsphere formulation AGM1 to AGM4 (a) and AGM5 to AGM8 (b)
Mentions: The in vitro diffusion of ALM from the prepared microspheres exhibited a biphasic mechanism. The release of ALM from the microspheres was characterized by an initial phase of burst effect due to the presence of drug particles on the surface of the microspheres followed by a second phase of moderate release. The initial burst effect is a desired effect to achieve initial therapeutic plasma concentration of the drug. The in vitro drug diffusion study from formulations AGM1 to AGM4 is presented in Figure 5a. As the concentration of CaCl2 and cross-linking time increased, percentage drug dissolved decreased. The in vitro drug diffusion study from formulations AGM5 to AGM8 are presented in Figure 5b. The decrease in percentage drug dissolved could be attributed to increase in the extent of cross-linking in the microsphere with an increase in the amount of cross-linking agent. The Ca2+ cross-linked microspheres form three-dimensional bonding structures with the GG inside the microspheres. This three-dimensional bonding results in extended cross-linking through the whole microsphere producing hard microcapsules with lower water uptake and thus leading to slow removal of drug in the dissolution media. The release of the drug has been controlled by swelling control release mechanism. In addition, the larger particle size at higher polymer concentration also restricts the total surface area thus resulting in slower drug release over a span of 8 h.

Bottom Line: Regression analysis was performed to identify the best formulation conditions.In vitro drug diffusion was Higuchi matrix controlled and the release mechanism was found to be non-Fickian.Stability studies indicated that there were no significant deviations in the drug content, in vitro mucoadhesion and in vitro drug diffusion characteristics.

View Article: PubMed Central - PubMed

Affiliation: Research Scientist, Formulation Development Department, Apotex Research Private Limited, Bangalore - 560 099, India.

ABSTRACT

Background: Almotriptan malate (ALM), indicated for the treatment of migraine in adults is not a drug candidate feasible to be administered through the oral route during the attack due to its associated symptoms such as nausea and vomiting. This obviates an alternative dosage form and nasal drug delivery is a good substitute to oral and parenteral administration.

Materials and methods: Gellan gum (GG) microspheres of ALM, for intranasal administration were prepared by water-in-oil emulsification cross-linking technique employing a 2(3) factorial design. Drug to polymer ratio, calcium chloride concentration and cross-linking time were selected as independent variables, while particle size and in vitro mucoadhesion of the microspheres were investigated as dependent variables. Regression analysis was performed to identify the best formulation conditions. The microspheres were evaluated for characteristics such as practical percentage yield, particle size, percentage incorporation efficiency, swellability, zeta potential, in vitro mucoadhesion, thermal analysis, X-ray diffraction study, and in vitro drug diffusion studies.

Results: The shape and surface characteristics of the microspheres were determined by scanning electron microscopy, which revealed spherical nature and nearly smooth surface with drug incorporation efficiency in the range of 71.65 ± 1.09% - 91.65 ± 1.13%. In vitro mucoadhesion was observed the range of 79.45 ± 1.69% - 95.48 ± 1.27%. Differential scanning calorimetry and X-ray diffraction results indicated a molecular level dispersion of drug in the microspheres. In vitro drug diffusion was Higuchi matrix controlled and the release mechanism was found to be non-Fickian. Stability studies indicated that there were no significant deviations in the drug content, in vitro mucoadhesion and in vitro drug diffusion characteristics.

Conclusion: The investigation revealed promising potential of GG microspheres for delivering ALM intranasally for the treatment of migraine.

No MeSH data available.


Related in: MedlinePlus