Bipolymeric Pectin Millibeads Doped with Functional Polymers as Matrices for the Controlled and Targeted Release of Mesalazine

Abstract

Targeted drug delivery systems are a very convenient method of treating inflammatory bowel disease. The properties of pectin make this biopolymer a suitable drug carrier. These properties allow pectin to overcome the diverse environment of the digestive tract and deliver the drug to the large intestine. This investigation proposed bipolymeric formulations consisting of the natural polymer pectin and a synthetic polymer containing the drug 5-aminosalicylic acid. Pectin beads were prepared via ionotropic gelation involving the interaction between the hydrophilic gel and calcium ions. The obtained formulations consisted of natural polymer, 5-aminosalicylic acid (5-ASA) and one of the synthetic polymers, such as polyacrylic acid, polyvinylpyrrolidone, polyethylene glycol or aristoflex. The release of the drug was carried out employing a basket apparatus (USP 1). The acceptor fluid was pH = 7.4 buffer with added enzyme pectinase to reflect the colon environment. The amount of the released drug was determined using UV-Vis spectrophotometry at a wavelength of λ = 330 nm. The kinetics of the drug dissolution revealed that none of the employed models was appropriate to describe the release process. A kinetic analysis of the release profile during two release stages was carried out. The fastest drug release occurred during the first stage from a formulation containing pectin and polyethylene glycol. However, according to the applied kinetic models, the dissolution of 5-ASA was rather high in the formulation without the synthetic polymer during the second stage. Depending on the formulation, 68–77% of 5-ASA was released in an 8-hour time period. The FTIR and DSC results showed that there was no interaction between the drug and the polymers, but interactions between pectin and synthetic polymers were found.

The Influence of the Hydrophobic Polymeric Coating on 5-ASA Release from the Bipolymeric Milibeads with Amidated Pectin

“…Moreover, the coating also affected the carrier stability. By comparing the presented results with the observation from our previous work [12], it was found that uncoated beads not containing the synthetic polymer decomposed faster. The coated formulations doped with synthetic polymers, particularly with PA, decayed slower, and beads F7 did not disintegrate completely, as was shown in Figure 3.…”

“…It may suggest that the chains of synthetic polymers interact with 5-ASA or/and with APN or/and with coating. The interaction between the COO-group from PA and the COO-group belonging to the drug, as well as the bond between PA and APN, were reported in our previous works [12,21]. The average surface area per mass of all formulations was analyzed, and the results were presented in Figure 2.…”

“…In the case of the release of 5-ASA from uncoated beads, the values of n were in the range from 0.30 ± 0.07 to 0.50 ± 0.07, meaning a Fickian diffusion mechanism. Only in the case of the release of 5-ASA from uncoated beads doped with PA the parameter of n was 0.65 ± 0.8 [ 12 ]. The obtained results in the present work suggest that the coating changes the mass transport mechanism.…”

“…The spectroscopic studies of pure ingredients of beads, uncoated formulations loaded and unloaded with the drug, as well as their corresponding physical mixtures, were carried out in our previous work [ 12 ]. In the present work, the investigation was mainly focused on the interaction between the polymer, PVAC-D, used as a coating, and other formulation ingredients.…”

“…The composition of coated pectin beads was presented in Table 1 . The procedure of the dry pectin beads preparation was described in our previous work [ 12 ]. Components of formulations were mixed with water using the homogenizer (CAT X120, Ballrechten-Dottingen, Germany) with the rotation speed of 20,000 rpm up to the homogenous solution was obtained.…”