Broad, Neville William;
(2005)
Content uniformity of intact pharmaceutical tablets by transmission near-infrared spectroscopy.
Doctoral thesis (Ph.D.), University College London.
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Abstract
Content Uniformity (CU) testing assures the active pharmaceutical ingredient (API) content within individual low dose units are within defined specifications. Primary techniques such as high performance liquid chromatography (HPLC) are typically employed for CU testing, where the API is separated from the otherwise interfering excipient matrix. Near-infrared spectroscopy (NIRS) is a rapid, non-destructive technique, where samples are analysed 'as is' and the resulting spectra usually contain many overlapping peaks due to interfering excipients. It is therefore a potential challenge to use NIRS for CU testing. Computer simulations showing the effect of product and analytical variation indicated that 0.1% of tablet batches at nominal potency would fail the British and United States Pharmacopoeial CU tests if the combined error of production variation and analytical precision are greater than 5.05% and 4.84% respectively. Transmission NIRS was evaluated for CU testing of a hormone steroid in single intact tablets (17.64% to 2.94% m/m) utilising development scale batches for calibration. Although measurements of an independent test sets gave prediction errors of < 2.5% RSD, a limited number of batches for calibration resulted in large relative errors at lower active concentrations. However, it was demonstrated for low dose Norvasc® tablets containing 2.5% m/m active that a transmission NIRS CU assay can be developed with relative prediction error of 1.44% RSD where there was sufficient inherent batch variation and specificity. A transmission NIRS method was transferred between NIRS instruments for the CU testing of Feldene® 20 mg Zydis® tablets (37.7% m/m Piroxicam) with a relative prediction error of around 0.7%. Measurements of an independent test set gave prediction errors < 1.3% RSD. Finally, a transmission NIRS conformance procedure was successfully developed for the in-process API content assurance within single Viagra® 50 mg tablets. This conformance method can be implemented rapidly at-line in analytical technology philosophy.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D. |
| Title: | Content uniformity of intact pharmaceutical tablets by transmission near-infrared spectroscopy. |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis Digitised by Proquest. |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10122299 |
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