Polyvinyl alcohol (PVA) copolymer is a relatively new pharmaceutical agent that was registered in the FDA Drug Master File in 2006. Hoshi et al.1 have utilised PVA for the development of PVA copolymer capsules, which are prepared first by copolymerizing acrylic acid (AA) and methyl methacrylate (MMA) on PVA as a skeleton and then using the obtained PVA copolymer as capsule shells. PVA copolymer capsules are a form of nongelatin capsule that present a series of advantages, such as low gas permeability, and can be particularly suitable for the encapsulation of hydrophilic solvents to enable the formulation of insoluble drugs, which is in turn expected to enhance bioavailability.
Often a factor neglected in drug development, the solubility of many compounds used in the formulation of potential new drugs is paramount since, although these compounds are expected to have a high clinical performance, they often fail to achieve it because of their low absorption in the gastrointestinal tract. It was following research indicating that the bioavailability of some insoluble drugs was enhanced when dissolved in polyethylene glycol (PEG) 400 (the solubility of a drug in PEG 400 is approximately 100 times higher than in water), that it became obvious to pharmaceutical manufacturers that dosage forms of insoluble drugs with PEG 400 could be developed, improving the solubility and thus the bioavailability of such entities. However, conventional hard capsules could not tolerate PEG 400: when gelatin capsules were filled with PEG 400, they became brittle and broke easily (the moisture in the shell was absorbed by PEG) and when hydroxypropyl methylcellulose (HPMC) capsules were filled with PEG 400, the agent oozed out through the capsule shell. Hoshi et al.1 decided then to focus on the manufacture of new synthetic polymers (resulting in the discovery of PVA copolymer) rather than natural polymers or polysaccharides as more suitable candidates for capsule shell materials.
The focus then turned to the electrostatic characteristics of PVA copolymer capsules, which were also investigated.2 Electrification is a well-known phenomenon that may cause problems, such as adhesion of the capsule during transport or dispersion of the capsule during the filling process. Of course, low electrification is desired and, on occasions, antistatic agents have been used to reduce electrification. The electrostatic characteristics of PVA copolymer capsules were determined using gelatin and nongelatin capsules as controls. Electrification was measured using the Faraday cage method and, of the three types of capsule studied, PVA copolymer capsules showed the lowest electrification value with negative electricity. Then, the surface potential charges of the three types of capsules were measured. Gelatin capsules gained the most charge and were characterized by positive electrification, while the PVA copolymer capsules displayed the lowest level of electrification and a negative charge; in fact, these capsules are not easily electrified and show easy attenuation of any electricity generated.
In conclusion, when compared with traditional gelatin capsules, PVA copolymer capsules are characterized, among other things, for presenting low water content, low electrification level and the capability of filling with hydrophilic solvent, potentially enhancing the bioavailability of insoluble drugs. Therefore, PVA copolymer and gelatin capsules should be treated as equivalent in drug development.
References
1. N. Hoshi, T. Ogura, T. Shimamoto and S. Uramatsu, Development of PVA copolymer capsules, Pharm. Tech. Eur., 16(4), 37¬–46 (2004).
2. N. Hoshi, A. Kida, T. Hayashi and Y. Murakami, Creating PVA copolymer capsules, Pharm. Tech. Eur., 20(6), 17–25 (2008).
Read the forthcoming issue of Pharmaceutical Technology Europe for a feature article on the potential application of PVA copolymer as a film coating agent for tablets and microparticles.
Written by Bibiana Campos-Seijo, Editor of Pharmaceutical Technology Europe
bcampos.seijo@advanstar.com
Ph: +44 (0)1244 393 258
Source: Pharmaceutical Technology Europe; www.ptemag.com/pharmtecheurope |
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