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An analytical investigation of the physiochemical properties of crushed rifapentine administered to paediatrics.
Thesis (MA)--Stellenbosch University, 2024.
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Stellenbosch : Stellenbosch University
2025
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| _version_ | 1867613844776419328 |
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| access_status_str | Open Access |
| author | Janse van Rensburg, Lisa Jane |
| author2 | Kellermann, Tracy |
| author_browse | Janse van Rensburg, Lisa Jane Kellermann, Tracy |
| author_facet | Kellermann, Tracy Janse van Rensburg, Lisa Jane |
| author_sort | Janse van Rensburg, Lisa Jane |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description |
Thesis (MA)--Stellenbosch University, 2024. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/131791 |
| institution | Stellenbosch University (South Africa) |
| last_indexed | 2026-06-10T12:42:35.472Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/131791 An analytical investigation of the physiochemical properties of crushed rifapentine administered to paediatrics. Janse van Rensburg, Lisa Jane Kellermann, Tracy Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine. Division of Clinical Pharmacology. Pediatric pharmacology Drugs -- Solubility Tuberculosis in children -- Treatment Drugs -- Administration UCTD Thesis (MA)--Stellenbosch University, 2024. ENGLISH ABSTRACT: Introduction: Tuberculosis (TB) remains a leading cause of mortality, particularly in paediatric populations where it accounts for a significant proportion of global TB burden. Rifapentine (RPT), a key antibiotic in TB treatment, poses challenges in paediatric care due to the lack of child-friendly formulations. Children under five years are often unable to swallow whole tablets, leading caregivers to resort to off-label practices like crushing tablets, which can significantly reduce the drug's bioavailability and therapeutic efficacy. This study aimed to investigate the physiochemical properties of crushed and dispersible RPT formulations and to explore potential interventions that could improve drug delivery and bioavailability in paediatric patients. Methods: A high-performance liquid chromatography (HPLC) method was developed and validated for the quantification of RPT. Three RPT formulations (Rifapentine 150 mg, Rifapentine 150 mg/Isoniazid 150 mg and Rifapentine 300 mg/Isoniazid 300 mg) were crushed and used to determine the aqueous solubility and stability in simulated gastric and intestinal fluid, with and without mechanical and chemical interventions. An extraction method was developed for RPT and used to evaluate its recovery in food and beverage products. The adsorption of crushed drug to a glass beaker and syringe walls was also analysed. The concentration and stability of a partial dose of a dispersible RPT tablet was assessed. Results and Discussion: The HPLC method developed for RPT quantification demonstrated robustness and accuracy across a calibration range of 0.156–10.0 μg/mL, with inter- and intra-day validations confirming precision within acceptable limits. Mechanical interventions and additives (cyclodextrin, NADES, ascorbic acid) improved RPT solubility, with effectiveness varying among formulations. Recovery of crushed RPT tablets from food and beverages was lower than the reference standard, with yogurt yielding the best results. Adsorption studies revealed that glass beakers minimized drug loss compared to syringes, and double rinsing further reduced drug lost due to adsorption. Stability in simulated gastrointestinal fluids varied among formulations, with ascorbic acid showing formulation-specific benefits. The new dispersible tablet formulation demonstrated challenges in achieving consistent dosing, with preparation method significantly influencing final concentrations. Conclusion: This study underscores the critical need for paediatric-specific RPT formulations that ensure adequate drug stability, solubility, and bioavailability. Crushing adult RPT tablets for paediatric use compromises drug efficacy, potentially leading to treatment failure and drug resistance. When crushing RPT tablets is necessary, using a glass beaker rather than a syringe for preparation and administration in liquid vehicles minimizes drug loss. Clinicians should advise caregivers to co-administer the crushed drug with high-fat foods to enhance absorption. Evaluation of the new investigational RPT dispersible tablet revealed challenges in achieving consistent and accurate dosing. The preparation method significantly influenced the final concentration, with dissolution in a glass beaker followed by a 5-minute equilibration period providing the most reliable results in the presence of INH. Future studies should evaluate syrups containing cyclodextrin, NADES, or similar carrier liquids which improve the solubility of the crushed RPT. This also provides an opportunity for flavour masking to make the formulation more tolerable to children. AFRIKAANSE OPSOMMING: Inleiding: Tuberkulose (TB) is 'n groot oorsaak van sterftes, veral onder kinders, waar dit 'n beduidende deel van die we reldwye TB-las uitmaak. Rifapentien (RPT), 'n sleutel-antibiotikum vir TB-behandeling, is uitdagend in pediatriese sorg weens 'n gebrek aan kinder-vriendelike formulerings. Kinders jonger as vyf kan dikwels nie heel tablette sluk nie, wat lei tot die vergruising van tablette – 'n praktyk wat die biobeskikbaarheid en terapeutiese doeltreffendheid van die geneesmiddel kan verminder. Hierdie studie het ten doel om die fisies-chemiese eienskappe van vergruisde en verspreibare RPT-formulerings te ondersoek en om intervensies te verken wat die aflewering en biobeskikbaarheid van die geneesmiddel in pediatriese pasie nte moontlik kan verbeter. Metodes: 'n HPLC-metode is ontwikkel en gevalideer vir die kwantifisering van RPT. Drie RPTformulerings (Rifapentien 150 mg, Rifapentien 150 mg/Isoniasied 150 mg, en Rifapentien 300 mg/Isoniasied 300 mg) is vergruis en gebruik om die waterige oplosbaarheid en stabiliteit in gesimuleerde maag- en intestinale vloeistof te bepaal, met en sonder meganiese en chemiese intervensies. 'n Ekstraherings metode is ontwikkel om die herwinning van RPT in voedsel- en drankprodukte te evalueer. Adsorpsie van vergruisde geneesmiddels aan glasbeker- en spuit wande is ook geanaliseer. Die konsentrasie en stabiliteit van 'n gedeeltelike dosis van 'n verspreibare RPT-tablet is beoordeel. Resultate en bespreking: Die ontwikkelde HPLC-metode vir RPT-kwantifisering het robuustheid en akkuraatheid getoon oor 'n kalibrasie-reeks van 0.156–10.0 µg/mL, met validerings wat presisie binne aanvaarbare perke bevestig het. Meganiese intervensies en bymiddels (siklodekstrien, NADES, askorbiensuur) het die oplosbaarheid van RPT verbeter, hoewel die effektiwiteit tussen formulerings verskil het. Herwinning van vergruisde RPT-tablette uit voedsel en drank was laer as die verwysings standaard, met jogurt wat die beste resultate gelewer het. Adsorpsie studies het getoon dat glasbekers geneesmiddel verlies minimaliseer in vergelyking met spuite, en dubbele uitspoeling het verdere verlies verminder. Stabiliteit in gesimuleerde spysverteringskanaal vloeistowwe het tussen formulerings verskil, met askorbiensuur wat spesifieke voordele getoon het. Die nuwe verspreibare tablet-formulering het uitdagings getoon in die bereiking van konsekwente dosering, met die voorbereidings metode wat finale konsentrasies aansienlik beï nvloed het. Gevolgtrekking: Hierdie studie beklemtoon die behoefte aan pediatriese-spesifieke RPTformulerings wat voldoende stabiliteit, oplosbaarheid en biobeskikbaarheid verseker. Die vergruising van volwasse RPT-tablette vir pediatriese gebruik kan die doeltreffendheid van die geneesmiddel kompromitteer, wat kan lei tot behandelings mislukking en geneesmiddel weerstand. Wanneer RPT-tablette vergruis moet word, minimaliseer die gebruik van 'n glasbeker vir voorbereiding en toediening in vloeistof voertuie die verlies van die geneesmiddel. Klinici moet versorgers adviseer om vergruisde RPT saam met hoe -vet voedsel toe te dien om absorpsie te verbeter. Evaluering van die nuwe verspreibare RPT-tablet het uitdagings in konsekwente dosering aan die lig gebring, met oplossing in 'n glasbeker en 'n 5-minute ekwilibrasie periode wat die mees betroubare resultate in die teenwoordigheid van INH verskaf het. Toekomstige studies moet strope ondersoek wat siklodekstrien, NADES, of soortgelyke draers bevat om RPT se oplosbaarheid te verbeter en smaak te maskeer vir beter verdraagsaamheid in kinders. Masters 2025-03-25T07:37:04Z 2025-03-25T07:37:04Z 2024-12 Thesis https://scholar.sun.ac.za/handle/10019.1/131791 Stellenbosch University xx, 138 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Pediatric pharmacology Drugs -- Solubility Tuberculosis in children -- Treatment Drugs -- Administration UCTD Janse van Rensburg, Lisa Jane An analytical investigation of the physiochemical properties of crushed rifapentine administered to paediatrics. |
| title | An analytical investigation of the physiochemical properties of crushed rifapentine administered to paediatrics. |
| title_full | An analytical investigation of the physiochemical properties of crushed rifapentine administered to paediatrics. |
| title_fullStr | An analytical investigation of the physiochemical properties of crushed rifapentine administered to paediatrics. |
| title_full_unstemmed | An analytical investigation of the physiochemical properties of crushed rifapentine administered to paediatrics. |
| title_short | An analytical investigation of the physiochemical properties of crushed rifapentine administered to paediatrics. |
| title_sort | analytical investigation of the physiochemical properties of crushed rifapentine administered to paediatrics |
| topic | Pediatric pharmacology Drugs -- Solubility Tuberculosis in children -- Treatment Drugs -- Administration UCTD |
| url | https://scholar.sun.ac.za/handle/10019.1/131791 |
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