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.

Improvement of Resveratrol Permeation through Sublingual Mucosa: Chemical Permeation Enhancers versus Spray Drying Technique to Obtain Fast-Disintegrating Sublingual Mini-Tablets

“…However, it is necessary to first evaluate the aptitude of RSV to cross the selected epithelial tissue by itself, as penetration and subsequent permeation phenomena are indispensable to ensure systemic effects. The main strategy to assess the permeability of an active ingredient through a biological membrane/tissue involves the use of a two-compartment open model (e.g., Franz-type diffusion cells) accompanied by a membrane that could be synthetic and accurately designed to simulate the biological tissue or could be a biological specimen [ 34 , 37 , 38 , 39 ]. Moreover, when evaluating the permeability of poorly water-soluble molecules, it is crucial to ameliorate their solubility into the donor compartment to increase the concentration gradient, which is indispensable in establishing the permeation phenomenon.…”

“…Similarly, the amount of drug entrapped (De) per unit area in the mucosal tissue was calculated at the end of each experiment following the relationship: where Q T is the amount of RSV (mg or μg) entrapped in the tissue and A is the area available for penetration (0.636 cm 2 ). The accumulation (A c ) was then calculated by the relationship: where C d is the starting RSV concentration loaded into the donor compartment [ 34 , 35 ]. The Origin 8.5 software was used for mathematical data processing.…”

“…where C d is the starting RSV concentration loaded into the donor compartment [34,35]. The Origin 8.5 software was used for mathematical data processing.…”

Chlorhexidine Mucoadhesive Buccal Tablets: The Impact of Formulation Design on Drug Delivery and Release Kinetics Using Conventional and Novel Dissolution Methods

“…The normal salivary flow rate is ≥1mL/min with a maximum value of 7 mL/min [ 21 , 22 ]. Drug release based on a controlled flow rate has previously been investigated elsewhere [ 44 , 45 , 46 , 47 ].…”

Solid and Semisolid Innovative Formulations Containing Miconazole-Loaded Solid Lipid Microparticles to Promote Drug Entrapment into the Buccal Mucosa

“…This parameter is related to the ability of the formulation to absorb water from the surrounding environment and swell, thus influencing film bioadhesion and drug release. Indeed, the amount of water absorbed must be the compromise between the development of the interactions through dosage form and mucosal mucins and the increase in the volume of the formulation, which, if excessive, could cause patient discomfort [ 37 ]. Formulations characterized by too high a swelling degree risk being too bulky, causing discomfort for the presence of an extraneous body in the oral cavity.…”