Characterizations of plasticized polymeric film coatings for preparing multiple-unit floating drug delivery systems (muFDDSs) with controlled-release characteristics

Abstract

Effervescent multiple-unit floating drug delivery systems (muFDDSs) consisting of drug (lorsartan)- and effervescent (sodium bicarbonate)-containing pellets were characterized in this study. The mechanical properties (stress and strain at rupture, Young's modulus, and toughness) of these plasticized polymeric films of acrylic (Eudragit RS, RL, and NE) and cellulosic materials (ethyl cellulose (EC), and Surelease) were examined by a dynamic mechanical analyzer. Results demonstrated that polymeric films prepared from Surelease and EC were brittle with less elongation compared to acrylic films. Eudragit NE films were very flexible in both the dry and wet states. Because plasticizer leached from polymeric films during exposure to the aqueous medium, plasticization of wet Eudragit RS and RL films with 15% triethyl citrate (TEC) or diethyl phthalate (DEP) resulted in less elongation. DEP might be the plasticizer of choice among the plasticizers examined in this study for Eudragit RL to provide muFDDSs with a short time for all pellets to float (TPF) and a longer period of floating. Eudragit RL and RS at a 1∶1 ratio plasticized with 15% DEP were optimally selected as the coating membrane for the floating system. Although the release of losartan from the pellets was still too fast as a result of losartan being freely soluble in water, muFDDSs coated with Eudragit RL and RS at a 1∶1 ratio might have potential use for the sustained release of water-insoluble or the un-ionized form of drugs from gastroretentive drug delivery systems.

Figure 1. Schematic illustration of the structure of the effervescent multiple-unit floating drug delivery systems (muFDDSs).

Figure 2. Theoretical plot of the pellet density versus the minimal elongation ratio of the pellet diameter based on (ε_d =  (d _P)^1/3).

Figure 3. Mechanical properties of wet-state films composed of ethyl cellulose and different grades of HPMC.

(A) Strain at breaking (%), (B) stress at breaking (MPa), (C) elastic modulus (MPa/%; slope), (D) toughness (MPa×%; AUC) (n = 4).

Figure 4. Water uptake plots of ethyl cellulose film samples plasticized with various plasticizers at 20% w/w and after adding 30% w/w of (A) HPMC 50 cps, (B) HPMC 4000 cps, (C) HPMC E10M, (D) HPMC K100M (n = 4).

Figure 5. SEM photos of pellets (B-RS TEC15) at various coating levels (w/w) of (A) 3%, (B) 6%, (C) 9%, and (D) 12%.

Figure 6. Photographs of pellets (A20-RL DEP15 20%) (A) and (A20–1S1L DEP15 20%) (B) after immersion in pH 1.2 buffer for specific times.

Figure 7. Effect of the coating level of Eudragit RL 30D (A) or Eudragit RL 30D RS 30D at 1∶1 (E) and different plasticizers on the time to float of pellets in pH 1.2 buffer at 37°C.

Floating patterns of the pellets coated with Eudragit RL 30D (B, C, and D) or Eudragit RL 30D: Eudragit RS 30D at 1∶1 (F) after immersion in pH 1.2 buffer at 37°C.

Figure 8. Losartan release profiles of formulations (A) A-RS TEC15 and A-Core, (B) B-RS TEC15 and B-Core, and (C) A20-RS TEC15 and A20-Core in pH 1.2 buffer.

Figure 9. Losartan release profiles of A20-Core and formulations (A) A20-RL TEC15, (B) A20-RL DEP15, (C) A20-RL DBP15, and (D) A20–1S1L DEP15 in pH 1.2 buffer.

(E) Effect of the coating membrane (Eudragit RL 30D: RS 30D at 1∶1 versus Eudragit RS 30D) on release profiles.