Validation of a Mathematical Model for the Description of Hydrophilic and Hydrophobic Drug Delivery from Biodegradable Foams: Experimental and Comparison Using Indomethacin as Released Drug

Abstract

In drug delivery systems, mathematical modeling plays an important role in elucidating the release mechanisms, the potential applications of a determinate system matrix–drug, or the design of new delivery systems. In this work, we have modeled porous biodegradable foams based on polylactide (PLA) and poly­(lactide-co-glycolide) (PLGA) impregnated with a hydrophobic drug (indomethacin) through a single-step process using supercritical CO2 as foaming agent. The modeling of indomethacin in vitro release was based on a previous model developed to describe accurately the process of release of a hydrophilic drug and consisting of three simpler and more comprehensible stages: external and internal mass transfer as well polymer degradation. It has been modified considering the low aqueous solubility of indomethacin and the variations in the mechanism produced, consequently improving its physical signification. Finally, the solubility of different drugs impregnated and their response in the release profiles were evaluated.

Polymer degradation and drug delivery in PLGA‐based drug–polymer applications: A review of experiments and theories

“…PLGA‐based products have been widely studied for controlled delivery of a variety of medicaments including macromolecular drugs (such as human growth factors, genes, peptides, proteins, vaccines, antigens, and so forth) and relatively small molecular drugs (hydrophilic/hydrophobic drugs). Since undesired pharmacokinetic properties have been associated with low aqueous solubility of the drug, the prediction of drug solubility is very important . As introduced before, Figure shows the typical example of release profiles of relative release amount of hydrophobic and hydrophilic drugs from PLGA‐based polymers.…”

“…As introduced before, Figure shows the typical example of release profiles of relative release amount of hydrophobic and hydrophilic drugs from PLGA‐based polymers. The degree of initial burst is much lower for hydrophobic drugs because their low aqueous solubility leads to a sustained low driving force …”

“…Since undesired pharmacokinetic properties have been associated with low aqueous solubility of the drug, the prediction of drug solubility is very important. 57 As introduced before, Figure 2 shows the typical example of release profiles of relative release amount of hydrophobic and hydrophilic drugs from PLGA-based polymers. The degree of initial burst is much lower for hydrophobic drugs because their low aqueous solubility leads to a sustained low driving force.…”

“…The degree of initial burst is much lower for hydrophobic drugs because their low aqueous solubility leads to a sustained low driving force. 57 There are numerous earlier studies to investigate the effects of drug type (hydrophilic or hydrophobic) on the degradation rate of PLGA matrices. For example, it has been reported that the diffusion (or swelling) rate of aspirin (relatively hydrophilic drug with aqueous solubility of 4.99 mg/mL) was substantially higher (i.e., 57.5 times) than that of haloperidol (relatively hydrophobic drug with aqueous solubility of 0.13 mg/mL).…”

“…86 introduced Eq. (17) in which D can be considered to be inversely proportional to M w , and the change of the M w was Diffusion coefficient: D 5 2.0 3 10 212 cm 2 s 21 5-Fluorouracil (5-FU) PLGA <36 Drug release amount: 56% (7 th day) 89 Drug release amount: 63% (7 th day) [56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72] Drug release amount: 73% (7 th day) Drug release amount: 87% (7 th day)…”