Oral formulation of combination therapies for ‎treatment of paediatric tuberculosis

Alsalhi, Alyaa Sulieman (2023). Oral formulation of combination therapies for ‎treatment of paediatric tuberculosis. University of Birmingham. Ph.D.

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Abstract

Tuberculosis is the main health issue worldwide and a disease that has raised the ‎mortality rate globally. Compliance with anti-tuberculosis (anti-TB) medication regime is ‎very low, especially regarding children. The bad taste of the drugs used to treat tuberculosis ‎is cited as a primary cause. This study has examined the multipatriculates dosage form ‎‎(spheroids- minitablets) of anti—TB drugs (isoniazid (INH), pyrazinamide (PZD), and ‎rifampicin (RIF), for children. Differential scanning calorimetry, the torque rheometer ‎MTR, and the stress control rheometer were used. In the first part of this study, the ‎rheological behaviours of wet powder masses were studied as a function of granulation ‎liquid (deionised water) and various grades of crospovidone (XPVP) and microcrystalline ‎cellulose (MCC). XPVP-CLM required more granulation liquid to reach the saturation for ‎extrusion-spheronisation (ES) stage compared to the standard MCC-PH101 grades with the ‎three anti-TB drugs.

In the second part of the study, XPVP-CLM-based spheroids were manufactured ‎using ES at ratios ranging between 10%-60% for the three drugs. XPVP-CLM was a robust ‎ES-aid with anti-TB drugs. Increasing the fraction of crospovidone led to the overall quality ‎of spheroids that were within the acceptable values of the quality target product profile ‎‎(QTPP). A high proportion of the aid led to uniform particles with acceptable physical and ‎mechanical features (friability, shape factor and flowability characteristic). The three drugs ‎were well distributed within the spheroids. ‎

The third section of this work has examined fluidized coating of the spheroids, and at ‎different film coating thicknesses. An increased thickness of film coating was needed to ‎mask the taste of isoniazid due to its high solubility. The final part of this work undertaken ‎has manufactured minitablets, to provide a better flexible dosage unit than spheroids. ‎Overall, the dose at different fractions of the three drugs showed acceptable values within ‎the standard value of the USP. Dosing was flexible by using different size commercial ‎capsules for the three anti-TB drugs. The taste-masked multiparticulate oral dosage form ‎can simplify the dosing regimen of the combined medicines to treat TB in children ‎compared to fixed-dose combination FDC.‎

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):