Amorphous Ropinirole-Loaded Mucoadhesive Buccal Film: A Potential Patient-Friendly Tool to Improve Drug Pharmacokinetic Profile and Effectiveness

Abstract

Nowadays the therapeutic strategies to manage Parkinson's Disease are merely symptomatic and consist of administering L-DOPA and/or dopamine receptor agonists. Among these, Ropinirole (ROP) is a widely orally-administered molecule, although it is extensively susceptible to hepatic metabolism. Since literature reports the buccal mucosa as a potentially useful route to ROP administration, the development of novel, effective, and comfortable oromucosal formulations should prove desirable in order to both enhance the therapeutic efficacy of the drug and allow a personalized therapeutic strategy able to meet the patient's needs. The results of the proposed ROP film as a new dosage form show that it is flexible; uniform; and characterized by suitable surface pH; good mucoadhesiveness; low swelling degree; and fast, complete drug release. Moreover, after ex vivo evaluation on a film having an area of 0.282 cm² and dose of 2.29 mg, the results of drug flux through the buccal mucosa are closely comparable to the amount of ROP that reaches the bloodstream at the steady-state condition after ROP-PR 4 mg oral administration, calculated according to the literature (0.237 mg/cm²·h^-1 vs. 0.243 mg/h, respectively). Moreover, drug flux and ROP dose could be accurately modulated time-by-time depending on the patient's need, by varying the administered disk area. In addition, the proposed ROP film displays no lag time, producing an immediate drug input in the bloodstream, which could result in a prompt therapeutic response. These findings make ROP film a potentially comfortable and patient-friendly formulation, and a promising candidate for further clinical trials.

Keywords: Eudragit® L100; Peppas-Salhin model; buccal administration; dissolution kinetics; ex vivo permeation; mucoadhesion; orocomucosal films; parkinson’s disease; ropinirole; therapy optimization.

Figure 1

Swelling degree and radial erosion studies of the ROP film: photographs of ROP film at the selected time intervals.

Figure 2

Differential Scanning Calorimetry (DSC) analysis: thermograms of pure crystalline ROP (black line) and ROP film (red line).

Figure 3

ROP release profile: percentage of drug released as a function of incubation time. The Peppas–Salhin fitting is highlighted together with the calculated fitting parameters.

Figure 4

Evaluation of the Fickian diffusional contribution (F) and the Case II relaxation/erosional contribution (R) in the Peppas–Salhin model: (A) variation of the Fickian diffusional contribution (F) and Case II relaxation/erosional contribution (R) as a function of time; (B) variation of the R/F ration as a function of time.

Figure 5

Mucoadhesion studies: relationship between contact time and detachment force (the standard error obtained results so small that the error bars are not visible in the graph).

Figure 6

ROP permeation profile through the buccal mucosa: mg/cm² of permeated drug as a function of time (●). The linear fitting at the steady state is highlighted (--).