(T1030-08-53) An Advanced Drug Delivery System for Enhancing Enteric Resistance and pH-Triggered Drug Release in the Duodenum

Purpose: Many oral products require enteric protection followed by rapid drug release to enable precise targeting within the proximal region of the small intestine. Drugs with a narrow absorption window are usually best absorbed in the duodenum and jejunum because of better solubility of drug in the upper than in the lower part of the GIT¹. Once the drug passes this absorption window, it is no longer able to be absorbed in the remaining parts of the gastrointestinal tract. This characteristic leads to reduced absorption of these drugs when taken orally, resulting in poor bioavailability. To address this issue, poly(meth)acrylate-based technology (EUDRATEC^® Fasteric) has been developed to protect acid-sensitive APIs, prevent gastric irritation by aggressive APIs, increase intestinal absorption and enhance bioavailability. This technology is based on a bilayer coating concept which consists of a modifying agent in the inner coating and anionic poly(meth)acrylate polymers in the outer layer. It has been specifically evaluated for different prototype drugs, including benazepril hydrochloride, metformin hydrochloride, L-methionine, and caffeine. The aim of this study was to assess technology’s performance with different biologically active ingredients across different categories, while also investigating the impact of trigger pH on the drug release profile.

Methods: For intermediate coating, a water suspension composed of modifying agent and hydroxypropyl methylcellulose was used. For caffeine pellets, water suspension of anionic poly(meth)acrylate polymer (EUDRAGIT^® L100 – as binder) and modifying agent were used. Trigger pH effect was demonstrated by varying the amount of modifying agent to adjust the drug release profile. For enteric coating, an aqueous dispersion of an anionic copolymer based on methacrylic acid and ethyl acrylate (EUDRAGIT^® L 30 D 55 - Evonik Industries AG, Darmstadt, Germany), with triethyl citrate (Vertellus LLC, Indianapolis, IN, USA) and talc (Imerys Talc S.p.A., Porte, Italy) was used. For caffeine tablets, an alternate enteric polymer (hypromellose phthalate HP-55) was used. Intermediate and enteric coating was done on different cores in fluidized bed processors (GPCG 1.1) for pellets and in perforated coating pan (Gans coater) for tablets and capsules. (formulation details in table 1) Analytical method: All other materials used for dissolution tests were of analytical grade. The coated formulation was analyzed for dissolution studies in 0.1 N HCl for 2 hours followed by drug release in pH 3.0 to 5.5 buffer for 1 hour at 50 rpm using a USP II (paddle) apparatus.

Results: All coated formulations achieved enteric resistance (not more than 10% drug release in 0.1 N HCl) followed by rapid drug release (not less than 80%) in pH 3.0 to 5.5 buffer at 45 min. 100% modifying agent in intermediate layer exhibited faster drug release profile as compared to lower concentration. (Fig. 2)

Conclusion: Application of EUDRATEC^® Fasteric coating technology has successfully demonstrated its ability to provide enteric resistance, followed by rapid and homogeneous pH release on four different prototype drugs. By adjusting the concentrations of modifying agent in intermediate layer, drug release profile can be modulated. This technology stands out for its simplicity and efficiency, offering significant flexibility in formulation while ensuring effective modulation of drug release.

Figure 1: Rapid duodenal release as a demonstration of functionality

Table 1: Formulation details

Figure 2: Dissolution profile of coated dosage forms in 0.1 N HCl followed by 3 different buffers