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Modulating Gliclazide Release and Bioavailability Utilizing Multiparticulate Drug Delivery Systems

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Abstract

Purpose

To formulate multiparticulate controlled-release alginate-gelatin (AL-GL) beads in order to modify gliclazide (GLZ) release rate.

Methods

AL-GL beads were prepared using different glutaraldehyde concentrations and dried using either air or freeze-drying method. For comparison, calcium alginate beads (AL-beads) were prepared at different temperatures. Drug incorporation efficiency, beads swelling%, drug release rate, and kinetics in gradient conditions (USP Apparatus-4) were studied. Selected AL-GL beads, as a test formulation (T), were in-vivo compared with Diamicron® 80 mg conventional tablet (R).

Results

AL-beads curing temperature was inversely proportional to GLZ incorporation efficiency and directly proportional to beads swelling%. GLZ release from AL-beads was slow in 0.1 N HCl and very fast in pH 7.4. In case of AL-GL beads, GLZ incorporation efficiency and swelling% were inversely proportional to glutaraldehyde concentration. AL-GL beads showed zero-order release of GLZ for up to 11 h. Scanning electron microscope (SEM) images of the freeze-dried beads showed a highly porous surface. Differential scanning calorimetry (DSC) and Fourier transform infra-red (FT-IR) studies indicated an interaction between alginate and gelatin due to crosslinking, while FT-IR indicated the absence of chemical interaction with GLZ. The relative bioavailability (T/R) was 97.57, 138.34, and 143.53%, for Cmax, AUC0–72, and AUC0–∞, respectively. Tmax of T was significantly higher than R.

Conclusion

AL-GL beads could represent promising delivery systems for modulating GLZ release rate and minimizing the variation in its absorption.

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Abbreviations

GLZ:

Gliclazide

AL-GL:

Alginate-gelatin

AL-High:

Alginic acid sodium salt-high viscosity

AL-Med:

Alginic acid sodium salt-medium viscosity

AL-low:

Alginic acid sodium salt-low viscosity

GA:

Glutaraldehyde

SEM:

Scanning electron microscope

DSC:

Differential scanning calorimetry

FT-IR:

Fourier transform infrared

ANOVA:

Analysis of variance

LLOQ:

Lower limit of quantification

HLOQ:

Higher limit of quantification

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Authors and Affiliations

  1. Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, 33 EL Bohouth St. (Former EL Tahrir St.).Dokki, Giza, Egypt

    Ebtesam W. Elsayed, Ahmed A. El-Ashmawy & Laila H. Emara

  2. Pharmacognosy Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, 33 EL Bohouth St. (Former EL Tahrir St.), Dokki, Giza, Egypt

    Khaled M. Mahmoud

  3. Department of Pharmaceutics, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt

    Nadia M. Mursi

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  1. Ebtesam W. Elsayed
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Supplementary Information

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12247_2021_9542_MOESM1_ESM.png

Supplementary file1 ESM_1: HPLC/UV chromatograms of GLZ in rat plasma; lower limit of quantification (LLOQ, 0.1 µg/ml) and higher limit of quantification (HLOQ, 10 µg/ml). (PNG 102 KB)

12247_2021_9542_MOESM2_ESM.jpg

Supplementary file2 ESM_2: Photographs of dried AL-beads; Viscosity grades: High (A), Medium (B) and Low (C). (JPG 385 KB)

Supplementary file3 ESM_3: Photographs of AL-GL beads; Key: A = Air-dried beads, B = Freeze-dried beads. (JPG 510 KB)

12247_2021_9542_MOESM4_ESM.jpg

Supplementary file4 ESM_4: DSC thermograms of pure GLZ, AL, GL, different blank AL-GL beads and GLZ loaded AL-GL beads. (JPG 1592 KB)

12247_2021_9542_MOESM5_ESM.jpg

Supplementary file5 ESM_5: FT-IR spectra of pure GLZ, AL, GL, different blank AL-GL beads and GLZ loaded AL-GL beads. (JPG 2594 KB)

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Elsayed, E.W., El-Ashmawy, A.A., Mahmoud, K.M. et al. Modulating Gliclazide Release and Bioavailability Utilizing Multiparticulate Drug Delivery Systems. J Pharm Innov 17, 674–689 (2022). https://doi.org/10.1007/s12247-021-09542-9

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