Performance of crosslinked POvidone as a solubilizer

For insoluble active pharmaceutical components (apis), increasing the dissolution rate is a major challenge in formulation development. The objective of this study was to evaluate the performance of several super disintegrators to improve the dissolution of drugs in wet pellet prescription. The insoluble meloxicam and fenofibrate were used as model drugs.

Depending on the amount prescribed, cross-linked Polyplasdone™ has been shown to significantly increase the dissolution rate of insoluble drugs in tablet formulations. The super disintegrators examined in this study are as follows:

Crosslinked Polyplasdone™; Another crosslinked povidone (1,2); Crosslinked sodium carboxymethyl cellulose; Sodium carboxymethyl starch; Low substituted hydroxypropyl cellulose (L-HPC)

Because the Polyplasdone™XL and Ultra specifications are identical in terms of physical and chemical properties (differing only in impurity content), they will be studied interchangeably in this article. The other cross-linked POvidone 1 and 2 differ only in particle size, and the interchange study was also carried out.

Test method

200mg meloxicam tablets were prepared by wet granulated method

Povidone Plasdone™K29/32 is dissolved in a batch of 20% ethanol. The milled meloxicam granules are sifted with various super disintegrators. Magnesium stearate and silica are added to the granules and mixed. The final mixture was pressed and the tablet weight was 200mg. The resulting tablets were determined for hardness, thickness, brittleness and disintegration time.

Preparation of 348mg fenofibrate Oral disintegrating tablets by wet granulation (20% super disintegrating agent)

Povidone Plasdone™K29/32 was dissolved in a batch of 15% ethanol, followed by the prescription amount of sodium dodecyl sulfate. The grinding finofibrate granules, various super disintegrators and peppermint flavor straighteners are sifted. Magnesium stearate and silica are added to the granules and mixed. The final mixture was pressed and the tablet weight was 348mg. The resulting tablets were determined for hardness, thickness, brittleness and disintegration time.

Preparation of 302.5mg fenofibrate Quick release tablets (8% super disintegrator) by wet pellet method

The preparation method of fenofibrate quick release tablets is the same as that of fenofibrate orally disintegrating tablets. The dissolution test method is the same as fenofibrate orally disintegrating tablets.

Results and discussion

1. Meloxicam tablets

The dissolution results of meloxicam tablets showed that tablets containing super disintegrators could meet the USP requirement of 30min to reach 70% drug release standard. Tablets that do not contain super disintegrators have the lowest drug release rate. Tablets with cross-linked Polyplasdone™XL-10 as disintegrators have the fastest drug release in pH7.5 buffers.

Figure 1. Dissolution results of Midloxicam tablets in pH7.5 phosphate buffer

2. Fenofibrate orally disintegrating tablets

FIG. 2 Dissolution results of Nonofibrate orally disintegrating tablets showed that tablets containing super disintegrating agents could meet the USP requirement of 70 percent drug release within 60 minutes. Tablets that do not contain super disintegrators have the lowest drug release rate. Tablets with cross-linked Polyplasdone™Ultra as disintegrator have the highest drug release in the pH7.5 buffer.

Figure 2. Dissolution results of nonofibrate orally disintegrating tablets at 0.025M sodium dodecyl sulfate

Figure 3 shows that fenofibrate does not meet the USP requirement of 70 percent drug release in 60 minutes. Figure 4 shows that fenofibrate orally disintegrating tablets have a higher drug release than rapid-release tablets. The amount of super disintegrant in fast release tablets is low.

Figure 3. Dissolution in 60min of 0.025M sodium dodecyl sulfate fenofibrate quick release tablets

Figure 4. Comparison of dissolution between tablets containing 20% and 8% super disintegrators

conclusion

The dissolution rate of insoluble drugs (meloxicam and fenofibrate) is significantly increased by the addition of super disintegrators to the prescription. In addition, tablets with crosslinked Polyplasdone™ had higher drug release levels than other super disintegrators, and fenofibrate tablets with higher levels of crosslinked Polyplasdone™ had higher drug release levels. On the basis of the data from this study, we recognize that cross-linked Polyplasdone™ can be used as a solubilizer to improve the dissolution of insoluble drugs.