Versatile and sensitive dual-detection HPLC method for rapid quantification of apomorphine hydrochloride: application to ex vivo percutaneous permeation and deposition studies utilising novel transdermal pressure-sensitive adhesive patches
Bibliographic record
Abstract
Abstract Conventional delivery of apomorphine hydrochloride (APO) for management of ‘OFF’ periods in Parkinson’s disease is limited to subcutaneous or sublingual delivery, and would substantially benefit from a transdermal drug delivery system (TDDS). Minimal progression has been made thus far in this area, with current literature presenting debatably flawed or inconsistent experimental design for ex vivo percutaneous permeation and deposition studies, a crucial step in understanding TDDS performance. Provided here is an improved, robust, versatile and easily-transferred analytical methodology, fully validated in accordance with guidelines provided by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). Reversed-phase high performance liquid chromatography (RP-HPLC) is employed with ultraviolet-visible (UV) light or fluorescence intensity (FID) detection in conjunction with a Franz diffusion-cell setup that ensures stability of APO and uses physiologically relevant neonatal porcine skin. Thus, this methodology may be reliably employed by future researchers developing an APO TDDS. To demonstrate application, a superficial investigation into model pressure-sensitive adhesive (PSA) patch systems provided sustained percutaneous delivery of up to 4.015 ± 2.361 µg/cm 2 /hr APO over a 24-hour period. These offer brief insight into a system that has yet to be studied in-depth for percutaneous delivery of APO, and highlight the importance of alternative penetration enhancers or enhancement techniques in developing a TDDS with clinical potential. Graphical abstract
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".