When drugs are encapsulated, electrification (the electrostatic charge of the capsule) may sometimes cause problems, such as capsule adhesion during transportation or dispersion of the capsule content in the filling process. In this article, the electrification of gelatin and nongelatin capsules is examined.

Polyvinyl alcohol (PVA) copolymer capsules are a form of nongelatin capsule under development. PVA, acrylic acid (AA) and methyl methacrylate (MMA) are used as raw materials. As previously reported, these capsules have advantages, such as low gas permeability, and can be particularly suitable for encapsulation of hydrophilic solvents, such as polyethylene glycol (PEG) 400, and surfactants.^1–5 Using such capsules facilitates the formulation of insoluble drugs and is expected to enhance bioavailability.

Key points

The electrostatic characteristics of PVA copolymer capsules were determined using gelatin and nongelatin (hypromellose (HPMC)) capsules as controls. After, the stability of a PVA copolymer capsule preparation of indomethacin (IND) solution was examined as a model of an insoluble drug preparation. In addition, the bioavailability of a sparingly water-soluble drug, acetaminophen, and a practically water-insoluble drug, nifedipin (NF), in both gelatin and nongelatin capsules was evaluated by administering the preparations to Beagle dogs.

Electrostatic characteristics⁶

It is well known that electrification of capsules has different characteristics depending on the raw material of the polymer compound used. Low electrification is desirable and there have been many cases where an antistatic agent was used to reduce capsule electrification. The electrostatic characteristics of three types of capsules were determined.

Table 1: Specific charges for the three capsule types per 1 g.

Measurement of electrification using the Faraday cage method. Approximately 2–3 g of each capsule type was measured out and placed in a Faraday cage (Advantest; Tokyo, Japan). The amount of triboelectricity generated by the capsules was measured with a digital multimeter (Advantest) and the specific charge electrification (nC/g) was calculated (Table 1). Of the three capsule types, the gelatin and HPMC capsules showed high electrification values with positive electricity. In contrast, the PVA copolymer capsule had the lowest electrification value with negative electricity.

Figure 1: Surface potential charge for the three capsule types.

Measurement of surface potential charges after generation of triboelectricity. Approximately 10 g of each capsule type was measured out, placed in a tablet friability tester. (Tsutsui Rikagaku Kikai; Tokyo, Japan). Triboelectricity was generated for 1 min and the surface potential charges of 20 randomly selected capsules were then measured using a surface charge electrometer (Model 1279, Monroe Electronics; NY, NY, USA) 5 and 10 min after the start of the test (Figure 1).

The gelatin capsules gained the most charge and were characterized by positive electrification. Additionally, their surface potential did not decrease easily. HPMC capsules are known to have less water content (~3%) than gelatin capsules (~15%) and their electrification tends to be lower. This tendency was confirmed in these experiments. However, the HPMC capsules showed a high level of surface potential, even after 10 min, and the charge tended not to attenuate easily. This phenomenon is considered to be a result of the low moisture content of the capsules.