Compounding of vitamin A, D₃, E and K₃ supplements for cystic fibrosis patients: formulation and stability study

Authors: Huyghebaert, N.¹; De Beer, J.²; Vervaet, C.¹; Remon, J. P.¹

Source: Journal of Clinical Pharmacy & Therapeutics, Volume 32, Number 5, October 2007 , pp. 489-496(8)

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Abstract:

Summary Background and objective:

Cystic fibrosis (CF) patients suffer from malabsorption of fat-soluble vitamins (A, D, E and K). These vitamins are available as water-dispersible (A, D₃ and E) or water-soluble grades (K₃), which is favoured in CF patients as they fail to absorb oil-based products. The objective of this study was to determine stability of these raw materials after opening the original package and to develop a compounded formulation of acceptable quality, stability and taste, allowing flexible dose adaptation and being appropriate for administration to children and elderly people. Methods:

The raw materials were stored after opening their original package for 8 months at 8 °C and room temperature (RT). Stability was assessed using a validated HPLC method after extraction of the vitamin from the cold water-soluble matrix (vitamin A acetate, D₃ and E) or using a spectrophotometrical method (vitamin K₃). These materials were mixed with an appropriate lactose grade (lactose 80 mfor vitamins A and D₃; lactose 90 m for vitamin E, lactose very fine powder for vitamin K₃) and filled in hard gelatin capsules. Mass and content uniformity were determined and stability of the vitamins in the capsules was assessed after 2 months storage at 8 °C and RT. Results:

All raw materials showed good stability during storage in the opened original package for 8 months storage at 8 °C as well as RT (>95% of the initial content). The compounded formulations complied with the requirements of the European Pharmacopoeia for mass and content uniformity and can be stored for 2 months at 8 °C or RT while maintaining the vitamin content between 90% and 110%. Conclusions:

As these fat-soluble vitamins are not commercially available on the Belgian market, compounded formulations are a valuable alternative for prophylactic administration of these vitamins to CF patients, i.e. a stable formulation, having an acceptable taste, allowing flexible dose adaptation and being appropriate for administration to children and elderly people.

Keywords: cystic fibrosis; oral formulation; stability; vitamin A; vitamin D3; vitamin E; vitamin K3

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2710.2007.00855.x

Affiliations: 1: Laboratory of Pharmaceutical Technology, Ghent University, Gent, Belgium 2: Scientific Institute of Public Health (Federal Public Service for Health, Food chain safety and Environment), Brussels, Belgium

Publication date: 2007-10-01