Dissolution Rate Enhancement of Entacapone and Formulation of its Oro- Dispersible Tablets: Applying Statistical Design

Abstract

The major aim of the study was to enhance the solubility and dissolution rate of entacapone by complexation with cyclodextrins (β-CD/HP β-CD). Further the selected cyclodextrin complexes are deigned to formulate oro-dispersible tablets (ODTs) using selected concentration of PEG 4000 as hydrophilic polymer and crospovidone as superdisintegrant. The phase solubility behavior of entacapone in presence of various concentrations of β-CD, HP β-CD, PEG 4000, PVP and Poloxamer 188 (0.25-5% w/v) was studied at 37 ± 2 o C. Gibbs free energy (∆G°t r ) values in negative, indicates the spontaneous nature of entacapone solubilization. From dissolution rate studies it was observed β-CD complexes were better over HP β-CD and are formulated to ODTs by direct compression method. Response surface modeling approach (2 3 full factorial design) was used for design, development and data interpretation. The responses of the design were analyzed using Design Expert 8.0.7.1 (Stat-Ease Inc., USA). The optimized formulation was selected on the basis of software analysis with an overall desirability factor. The optimized formulation showed disintegration time of 40-42s, friability of 0.55% and a release of more than 85% within 45 m. The physicochemical characterizations of inclusion complexes and the optimized tablet formulation were done by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD).

Entacapone Polymorphs: Crystal Structures, Dissolution, Permeability, and Stability

“…4 However, because of the low solubility of ETP 0.08 mg/mL (80 μg/mL) 5 and apparent permeability log P app of 0.18 ± 0.02 cm/s, 6 the drug is practically insoluble in water and categorized under Biopharmaceutics Classification System (BCS) class IV. 7 The wide use of entacapone tablets, either in single dose or as a combination therapy, means it is important to have a detailed understanding of the different crystalline forms (polymorphs) of entacapone.…”

Entacapone: Improving Aqueous Solubility, Diffusion Permeability, and Cocrystal Stability with Theophylline

“…13 However, ETP is a Biopharmaceutics Classification System (BCS) Class IV drug and exhibits erratic oral bioavailability. 14 This problem is attributed to poor aqueous solubility, low membrane permeability, and first pass metabolism. The aqueous solubility of ETP is less than 80 μg/mL at pH ≤ 5.0 but rises with increasing pH.…”

Tablet Geometry Effect on the Drug Release Profile from a Hydrogel-Based Drug Delivery System

“…It means that the drug release profile can be predicted with high accuracy only by knowing the type of geometry and its dimensions without conducting numerous dissolution tests. Although such a result has been obtained for variables such as formulation [ 13 , 30 , 32 ] or appearance properties and variables related to drug production [ 31 , 32 , 33 ] with an experimental approach in previous studies, based on our knowledge, these results for different types of geometries and their dimensions have not been mentioned in previous studies. Another result was that while having common features of tablets such as surface-to-volume ratio or maximum tablet length, regardless of the type of geometry and despite the significant effect of all these common features on release profile responses, it is not possible to have a powerful prediction of the drug release profile.…”

“…Most of the studies conducted in this field are related to the effect of drug formulation [ 13 , 30 , 31 , 32 ] or the effect of appearance properties or characteristics related to drug production, such as tablet coating weight, porosity, dimensions of particles, the pressure of the tablet compression machine, or many other properties [ 31 , 32 , 33 ]. One of the factors that can affect the release rate is the geometry of the matrix.…”