Using Polymer Technology to Enhance Bioavailability - Pharmaceutical Technology

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Using Polymer Technology to Enhance Bioavailability
The authors review seven polymer classes that can be used to prepare solid-dispersion formulations.


Pharmaceutical Technology
pp. s37-s42

Cationic methacrylate is a cationic copolymer of dimethylaminoethyl methacrylate, methacrylate methylester, and methacrylate butylester. Cationic methacrylate is soluble in gastric fluid as well as weakly acidic buffer solutions up to pH 5 (8). The cationic dimethylaminoethyl methacrylate substituent group can provide a unique ionic interaction with APIs for solid-dispersion technology. This ionic interaction is believed to further stabilize solid solutions beyond hydrogen bonding and steric interactions. The methacrylate ester groups are considered to be good hydrogen-bond accepting groups for hydrogen-bond donating APIs. However, the strong cationic interaction can be detrimental to drug stability when the drug is susceptible to common cation catalyzed reactions.

Cationic methacrylate is soluble in methanol, ethanol, isopropanol, acetone, dichloromethane, ethyl acetate and various other solvents making it a suitable solvent for spray-drying application (8). The low glass-transition temperature of the polymer (48 C) makes it difficult to use in spray-drying applications but makes it ideal for use in hot-melt extrusion processing.

Methacrylic acid copolymers Type A and Type B are anionic copolymers of methacrylic acid and methyl methacrylate. The Type A copolymer has a ratio of 1:1 of each monomer unit whereas the Type B copolymer has a ratio of 1:2 of the methacrylic acid monomer to the methyl methacrylate monomer. The Type A copolymer is reportedly soluble/permeable in intestinal fluid from pH 6 and higher; whereas, the Type B copolymer is reportedly soluble/permeable in intestinal fluid from pH 7 and higher (8). The methacrylic acid monomer unit in these copolymers is capable of donating hydrogen bonds to APIs with hydrogen bond accepting groups. The methyl methacrylate monomer unit is capable of accepting hydrogen bonds from APIs with hydrogen bond donating groups. These hydrogen bond donating and hydrogen bond accepting properties make methacrylic acid copolymers versatile for solid dispersion technology. However, the strong anionic interactions can be detrimental to drug stability if the API is susceptible to anion catalyzed reactions.

The Type A and Type B anionic copolymers remain soluble in methanol, ethanol, isopropanol, and acetone. This solubility makes them suitable for solvent-based spray drying (8). It is not possible to determine the glass-transition temperatures of Type A and B copolymers because the functional groups become damaged at temperatures greater than 150 C (8). Plasticizers must be used to successfully melt extrude these polymers and barrel temperatures must be effectively controlled to prevent polymer degradation. Triethyl citrates, polyethylene glycols, acetyl triethyl citrate, some butyl citrates, polysorbates, dibutyl sebacate, triacetin, and 1,2-propylene glycol can be used to plasticize these copolymers (8). For spray- drying application, these polymers' high glass-transition temperatures aids in producing good particle size with good product yield.

Methacrylic acid copolymer Type C is an anionic copolymer of methacrylic acid and ethyl acrylate in a 1:1 ratio, that also contains 0.7% sodium lauryl sufate and 2.3% polysorbate 80, as emulsifiers (9). This copolymer mixture is reportedly soluble/permeable in intestinal fluid at pH ranges of 5.5 and higher (8). Similar to Type A and B copolymers, the Type C copolymer is capable of donating hydrogen bonds through the methacrylic acid monomer unit and can also accept hydrogen bonds through the ethyl acrylate monomer unit. These anionic interactions, however, can be detrimental to drugs that are susceptible to anion catalyzed reactions.

The Type C anionic copolymers are soluble in ethanol, methanol, isopropanol, and acetone but insoluble in dichloromethane (8). These solvents are also suitable in spray-drying applications. Their lower glass-transition temperature (110 C) makes the copolymer mixture ideal for spray-drying application and melt-extrusion processing. If necessary, plasticizers such as those compatible with Type A and Type B copolymers can be added to increase melt-extrusion throughput.


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