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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

Response surface plots for the (a) Effect of drug: Polymer ratio (X1) and calcium chloride (CaCl2) concentration (X2), (b) Effects of CaCl2 concentration (X2) and cross-linking time (X3) and (c) Effect of drug: Polymer ratio (X1) and cross-linking time (X3) On particle size
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Figure 7: Response surface plots for the (a) Effect of drug: Polymer ratio (X1) and calcium chloride (CaCl2) concentration (X2), (b) Effects of CaCl2 concentration (X2) and cross-linking time (X3) and (c) Effect of drug: Polymer ratio (X1) and cross-linking time (X3) On particle size

Mentions: Three-dimensional response surface plots generated by the Design Expert® software are presented in Figures 7 and 8 for the studied responses that is, particle size and in vitro mucoadhesion, respectively. Figures 7a depicts response surface plot for the effect of drug: Polymer ratio (X1) and CaCl2 concentration (X2) on particle size, which indicate a linear effect on particle size of the microspheres. The combined effects of CaCl2 concentration (X2) and cross-linking time (X3) and drug: Polymer ratio (X1) and cross-linking time (X3) on particle size, as shown in Figure 7b and c also revealed linearity. This explains that the higher the amount of CaCl2 or higher the time of cross-linking, the more will be the cross-linking of the guluronic acid units of GG leading to the formation of larger microspheres.


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)

Response surface plots for the (a) Effect of drug: Polymer ratio (X1) and calcium chloride (CaCl2) concentration (X2), (b) Effects of CaCl2 concentration (X2) and cross-linking time (X3) and (c) Effect of drug: Polymer ratio (X1) and cross-linking time (X3) On particle size
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Response surface plots for the (a) Effect of drug: Polymer ratio (X1) and calcium chloride (CaCl2) concentration (X2), (b) Effects of CaCl2 concentration (X2) and cross-linking time (X3) and (c) Effect of drug: Polymer ratio (X1) and cross-linking time (X3) On particle size
Mentions: Three-dimensional response surface plots generated by the Design Expert® software are presented in Figures 7 and 8 for the studied responses that is, particle size and in vitro mucoadhesion, respectively. Figures 7a depicts response surface plot for the effect of drug: Polymer ratio (X1) and CaCl2 concentration (X2) on particle size, which indicate a linear effect on particle size of the microspheres. The combined effects of CaCl2 concentration (X2) and cross-linking time (X3) and drug: Polymer ratio (X1) and cross-linking time (X3) on particle size, as shown in Figure 7b and c also revealed linearity. This explains that the higher the amount of CaCl2 or higher the time of cross-linking, the more will be the cross-linking of the guluronic acid units of GG leading to the formation of larger microspheres.

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