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Preparation and Characterization of pH-Independent Sustained-Release Tablets Containing Hot Melt Extruded Solid Dispersions of Clarithromycin

Tablets Containing Solid Dispersions of Clarithromycin

  • Research Article
  • Theme: Advancements in Amorphous Solid Dispersions to Improve Bioavailability
  • Published:
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Abstract

The limited solubility of clarithromycin (CAM), coupled with low bioavailability and rapid elimination, are major shortcomings, needed to be addressed to achieve optimum therapeutic goals. Therefore, sustained-release (SR) tablets containing solid dispersion (SD) granules of CAM were prepared in this study. Initially, SD granules of CAM were prepared by hot melt extrusion (HME) technique using Kollidon VA64 as a hydrophilic carrier. The saturation solubility of SD showed almost 4.5-fold increase as compared to pure CAM in pH 6.8 medium. In vitro drug dissolution data indicated a substantial increase in the dissolution of SD as compared to that of pure CAM. The thermal stability of drug, carrier, and SD at elevated HME temperatures was evident from the results of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Powder X-ray diffraction (PXRD) data and scanning electron microscope (SEM) images revealed a decrease in the crystallinity and the uniform dispersion of drug, respectively. Moreover, Fourier transformed infrared spectroscopy (FT-IR) data confirmed the formation of hydrogen bond between the carbonyl group of drug and the hydroxyl group of carrier. SD loaded sustained-release (SD-SR) matrix tablets were prepared with hydrophobic polymers (Eudragit RS100 and Eudragit RL100). The pH-independent swelling and permeability of both polymers were responsible for the sustained drug release from SD-SR tablets. Pharmacokinetic (PK) studies suggested a 3.4-fold increase in the relative bioavailability of SD-SR tablets as compared to that of pure CAM.

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Abbreviations

BBD:

Box-behnken Design

BS:

Backscarttering

CFU:

Colony-Forming unit

CL_NP:

Cluser of nanoparticles

Coated_LGG:

Coated Lacticaseibacillus rhamnous GG

CPPs:

Critical process parameters

CQAs:

Critical quality attributes

CTRL:

Control

DLS:

Dynamic light diffusion

DoE:

Design of the experiment

EDL:

Electric double layer

LAB:

Lactic acid bacteria

LGG:

Lacticaseibacillus rhamnous GG

MCs:

Micricapsules

NPs:

Nanoparticles

PCs:

Photon correlation spectroscopy

PDI:

Polydispersity index

QTTP:

Quality target profile

SD:

Standard deviation

T:

Transmission

TEM:

Transmission electron microscopy

TSI:

Turbiscan Stability Index

TSS:

Total soluble solids

ZP:

Zeta potential

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Funding

Authors would like to acknowledge Higher Education Commission of Pakistan for providing funds to Mr. Qazi Amir Ijaz (pin no. 50021487).

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Authors and Affiliations

  1. Punjab University College of Pharmacy, University of the Punjab Lahore, Lahore, Pakistan

    Qazi Amir Ijaz, Qurat-ul-ain Shoaib, Memoona Rashid, Amjad Hussain, Nadeem Irfan Bukhari & Nasir Abbas

  2. Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University, Lahore, Pakistan

    Sumera Latif

  3. Faculty of Pharmacy, Department of Pharmaceutics, Bahauddin Zakaria University, Multan, Pakistan

    Muhammad Sohail Arshad

  4. Akson College of Pharmacy, Mirpur University of Science & Technology, Mirpur AJ &K, Mirpur, Pakistan

    Sohail Riaz

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  1. Qazi Amir Ijaz
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Ijaz, Q.A., Latif, S., Shoaib, Qua. et al. Preparation and Characterization of pH-Independent Sustained-Release Tablets Containing Hot Melt Extruded Solid Dispersions of Clarithromycin. AAPS PharmSciTech 22, 275 (2021). https://doi.org/10.1208/s12249-021-02115-6

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