Vitamin A Oral Liquid Preparation

In accordance with the Rules and Procedures of the 2010–2015 Council of Experts, Monographs Dietary Supplements Expert Committee has revised the Vitamin A Oral Liquid Preparation. The purpose for the revision is three fold:

1. Move the monograph to the Drug section of USP with a cross reference in the Dietary Supplement Section of the USP.
2. Revise the language of the analytical procedure to avoid errors of overestimation of the dose actually delivered.
3. Introduction of a new reference standard for retinyl palmitate.

Background:

This article should be categorized as a drug with a cross reference in the dietary supplements section of USP, because it is delivered in high doses (100,000 200,000 IU) in WHO health programs. This level of dose is considered a pharmaceutical product in many countries around the world. Vitamin A Oral Liquid Preparation is used in fact to prevent diseases derived from vitamin A deficiency, and ultimately the death of children caused by common childhood infections. The sponsor has indicated that twice yearly provision of high dose vitamin A by their programs have shown to reduce the all cause mortality in children under 5 years old by 23%. The high dose vitamin A is also used in the treatment of measles, acute malnutrition and prevention of blindness by xerophthalmia.

The sponsor has requested a modification of the language in the analytical procedure based on the results of testing of several batches of capsules as containers of the Vitamin A Oral Liquid Preparation in USP laboratories and in the manufacturer's quality control labs. These results have shown that 10% of the material remains inside of the capsules, and it is not actually delivered under the typical conditions of use. The experiments have shown that when the weight of Oral Preparation is 13% higher when determined by difference between full capsules and empty capsules versus when it is determined by direct weight.

The proposal is to modify the language of the sample preparation in the monograph as follows:

and similarly in the test for content uniformity:

Finally, USP currently has no reference standard for retinyl palmitate. USP Vitamin A Reference Standard is a solution of 30 mg of retinyl acetate per g of peanut oil. Currently, all analytical determinations of retinyl palmitate are conducted using retinyl acetate as the molar response factors are the same for both compounds. A new reference material for retinyl palmitate has been developed to address these issues. This material has been stabilized and packaged in sealed ampules under inert atmosphere. Thus, the Monographs Dietary Supplements Expert Committee proposes modifications to the monograph to use this new reference material in the analysis of Oral Liquid Preparations containing retinyl palmitate as the active ingredient.

The Vitamin A Oral Liquid Preparation Revision Bulletin supersedes the monograph for Vitamin A Oral Liquid Preparation currently published in Second Supplement to the USP 33–NF 29 Reissue. The Revision Bulletin will be incorporated in USP 34–NF 29.

Should you have any questions, please contact Natalia Davydova, Ph.D. (301-816-8328 or nd@usp.org.)

• Download the Vitamin A Oral Liquid Preparation Revision Bulletin

* May 27, 2011 update: The Vitamin A Oral Liquid Preparation Revision Bulletin was originally scheduled to be incorporated and moved to the Drug section in USP 34–NF 29. The revised monograph was incorporated in USP 34–NF 29, but did not move to the Drug section at that time.