Issue link: https://www.e-digitaleditions.com/i/962670
Tablets & Capsules April 2018 27 Figure 4 Dissolution of a BCS Class I sparingly soluble API using an ion exchange resin in simulated saliva (pH 6.2, 1:1 resin-to-API weight ratio) API standard API-IER resinate Time (seconds) Concentration (mg/L) 1,200 1,000 800 600 400 200 0 0 200 400 600 800 1,000 1,200 1,400 Figure 3 Equilibrium reaction mechanism between ion exchange resin and API Resin Resinate R = resin - = resin functional group ion A + = resin counter ion API + = drug ion X - = drug counter ion + API + X - Resin - A + + API + X - Resin - API + + A + X - A + API + A + API + A + API + A + A + A + A + API + A + API + A + API + A + API + API + API + API + A + API + - - - - - - - - - - - - - - - - - - - - - - R R Barrier membrane polymer coatings A barrier membrane polymer coating can provide acceptable taste masking and palatability depending on the API's particle size, particle size distribution, and morphology as well as the coating composition and film thickness. Applying the polymer coating directly to API particles or API-layered substrates is the most common and well understood method for taste masking a bitter API [2]. The polymer is applied via spraying or powder layering to form a barrier membrane to the substrate, reducing or eliminating API release within the patient's mouth. Fluid-bed coating is often the unit operation of choice for this type of application because it's efficient; applicable to particles, granules, and layered substrates; provides a uniform, continuous product coating; can be used in aqueous, organic coating, and powder layering applications; and is suitable for containment of potent compounds. In a series of studies, Colorcon researchers combined a water-insoluble ethylcellulose dispersion type B NF coating (Surelease) and a water-soluble hypromellose- based coating (Opadry) at ratios of 80:20, 85:15, and 90:10 Surelease-to-Opadry (w/w) and applied the resulting combination coatings to a BCS Class I sparingly soluble API granule or layered substrate [3, 4]. In the case of the layered substrate, successive layers of API and coating were applied to a sugar sphere (Suglet) resulting in a taste-masked multiparticulate bead, as shown in Figure 1. The researchers coated the API-layered multi- particulates to 4 or 5 different weight-gain (WG) levels between 20 and 40 percent, applying a seal-coat between the API layer and the functional layer to protect the API layer from erosion and moisture and provide a uniform application surface for the functional layer. (Depending on the extent of desired taste masking and the API release profile, a swellable component can be added to this seal-coating layer to aid in rupturing the barrier membrane coating.) The dissolution profiles for the coated multi- particulates are shown in Figures 2a, b, and c. The results illustrate how, when either the coating thickness (percent WG) or the percentage of water insoluble polymer is increased, initial API release is slowed and terminal release is extended. While taste-masking applications strive for minimal to no API release in the patient's mouth, they often also require immediate release functionality to achieve bioequivalence. These study results demonstrate how formulators can achieve effective taste masking with an initial lag in API release yet still retain the desired immediate-release behavior. Ion exchange resins Ion exchange resins (IERs) are insoluble polymers with acidic or basic functional groups, capable of exchanging counter-ions with surrounding media, as shown in Figure 3. In industrial and domestic water treatment, this ion exchange involves low-molecular-weight minerals such as calcium and magnesium (demineralization). In the pharmaceutical industry, this exchange applies to larger organic ions with molecular weights up to several hundred daltons and occurs both in vitro and in vivo. IERs are insoluble in all solvents and at all pH values, which, combined with their high molecular weight, prevents them from being absorbed by the body and makes them safe and nontoxic. Pharmaceutical developers have been using IERs for many years as both excipients and pharmacologically active ingredients. IERs can perform several functions, including modifying API release, taste masking, and improving API stability, and they are suitable for a variety of solid oral dosage forms, including ODTs, chewable tablets, fast-melt formulations, thin film strips, gums, gummies, and stick packs as well as liquid formulations. IERs are effective for taste masking because the API- IER complex (called the resinate) is insoluble, which prevents the API from directly contacting the taste buds.