Preparation andin vitroevaluation of propylthiouracil microspheres made of Eudragit RL 100 and cellulose acetate butyrate polymers using the emulsion-solvent evaporation method

Abstract

The objectives of this investigation are to evaluate the encapsulation efficiency of the anti-thyroid agent 6-n-propyl-2-thiouracil using two polymers of different characteristics (cellulose acetate butyrate polymer, (CAB-551-0.01) and ammonio methacrylate copolymer (Eudragit RL 100) and to study the effect of this encapsulation on the drug release properties. Polymers were used separately and in combination to prepare different microspheres. Also, the effect of polymer solution phase viscosity was studied for each of the polymers and for their combinations. An Ostwald viscometer was used to evaluate the relative viscosities of polymer solution phases and their combinations. Microspheres with 25% theoretical drug loading of 6-n-propyl-2-thiouracil core material were prepared by the emulsion solvent evaporation method. Microspheres prepared from CAB-551-0.01, which has higher relative polymer phase viscosity than Eudragit RL 100, showed significantly lower drug release rates and a noticeable lag time. Polymer combinations of CAB-551-0.01 and Eudragit RL 100 (1:1) showed an interesting synergistic increase in relative polymer solution viscosities at all concentrations. Unlike microspheres prepared from the two polymers separately which follow Higuchi spherical matrix release kinetics, microspheres prepared using a combination (1:1) of the two polymers showed near zero order with faster rates compared to those prepared using CAB-551-0.01 equivalent polymer concentrations. The results of this study suggest that 6-n-propyl-2-thiouracil was successfully and efficiently encapsulated and release rates of matrix microspheres are related to polymer solution phase viscosity, but when polymer combinations were used other factors such as structural effects must be considered.

Zero-order release formulations using a novel cellulose ester

“…Other cellulose esters used in drug delivery, cellulose diacetate (Cellulose Acetate, NF; referred to as CA in this paper) and cellulose acetate butyrate (Cellaburate, NF in 2010; referred to as CAB in this paper), are water insoluble and pH insensitive. They are used primarily as part of the coatings for tablets in osmotic pump devices (Santus and Baker 1995), as taste masking agents, or in matrix formulations provided other water-soluble excipients are present (Bodmeier and Siepmann 1999;Obeidat and Price 2005). This paper describes studies of a new cellulose ester, carboxymethylcellulose acetate butyrate (CMCAB) for use in pharmaceutical formulations as the main matrix resin.…”

Inhibiting the Gastric Burst Release of Drugs from Enteric Microparticles: The Influence of Drug Molecular Mass and Solubility

“…In in vitro dissolution tests, enteric formulations may release no more than 10% of their drug content during a two-hour incubation in 0.1N HCl, and subsequently should release more than 80% of their drug content within 45 min of changing the dissolution medium to intestinal conditions. While drug release in intestinal conditions is easily achieved given that readily suspended microparticles have a large surface area, minimising/inhibiting drug release in acidic conditions has proven challenging, and insufficient control of drug release from microparticles in acid media has been reported [4][5][6][7][8][9][10] .…”

Enteric Controlled-Release Pantoprazole-Loaded Microparticles Prepared by Using Eudragit S100 and Poly(ε-caprolactone) Blend

“…[5,14,15] Anhydrous systems have been used to produce microparticles using O/O emulsions. [14,[16][17][18][19][20] This technique consists of an organic phase containing the polymer emulsified with an immiscible oil. The use of anhydrous systems can lead to higher drug entrapment efficiency and higher yields than conventional O/W emulsions.…”