Document mpb4R9E1wodVyVm73NrjmKeaZ

Evaluation of stability data of calcium pantothenate in a vitamin food supplement packaged in blister Aclar / Aluminium We would like to provide an example of a multivitamin and multimineral food supplement formulated for women after giving birth, especially for breast feeding women. These capsules are packed in PCTFE containing blisters (Aclar/ aluminium). Each capsule contains pantothenic acid in the form of calcium pantothenate (vitamin B5). The calcium pantothenate has a 40% overage in order to compensate for the loss during product stability and to comply with the specifications 90% - 175% label claim. The pantothenic acid added as calcium pantothenate, has been chosen as a marker for water ingression in the aclar/aluminium blister, as panthotenate decomposes by hydrolysis (1). This means it is very sensitive to water presence and water permeation through the blister needs to be avoided. Pantothenic acid can serve as marker for the moisture permeation and overall stability of the food supplement formulation. Shelf-life studies of two batches Two industrial batches: MA02CH5 and MA02CH6 were manufactured for stability testing and the pantothenic acid stability was determined according to ICH (International council for harmonization) guideline (ICH STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS Q1A(R2) for the condition of 25C/60% RH, ICH Q1F for the condition 30C/75% RH). Stability at ICH Condition 25C/60% RH* * RH = relative humidity The blister secures 36 months shelf-life at the 25C/60% RH, as it complies with the specification. 1 Stability at ICH Condition 30C/75% RH Pantothenic acid stability at 30C/75% RH in blister aclar/aluminium foil Specification 90% -175% Pantothenic acid % label claim 7 mg 170 160 150 140 130 120 110 100 90 80 0 3 6 9 12 15 18 21 24 Time in months MA02CH5 MA02CH6 A greater degradation was detected at higher temperatures and humidities. Here, the blister secures 18 months shelf-life at the 30C/75% RH. At the next timepoint (24 months) the pantothenic acid does not comply with the specification (90%, red line in diagram). Alternative blister packaging materials The Aclar material is chosen as it provides a very good barrier to moisture and is used widely for the blister packaging of pharmaceuticals and food supplements. Moisture barrier of different films (2) Material film PVC (polyvinyl chloride) PVC/PVDC polyvinyl chloride (PVC) coated with polyvinylidene chloride (PVDC) PVC/PCTFE polyvinyl chloride (PVC) coated with polychlorotrifluoroethylene (PCTFE) Aclar PP polypropylene Thickness in microns 254 254 & 31 Water vapor transmission rate (g/m2/day) at 20C/85% RH 1.1 0.17 203 & 19 0.07 305 0.20 2 PCTFE Homopolymers. Honeywell (Morristown NJ, USA) produces Aclar UltRX 3000 Film material PVC/PVDC PVC/PCTFE Reduction on moisture transmission relativecompared to PVC 5 to 10 15 Currently we as downstream user are not aware of available alternatives to the PVC/PCTFE blister film that provide the needed moisture protection for our above mentioned multivitamin and multimineral food supplement. Discussion A replacement of the PVC/ Aclar material in blister for other more moisture permeable materials like PVC, PVC/PVDC or PP will provide inferior protection from moisture to the formulation, which will result in faster degradation of e.g. panthotenic acid and a shorter shelf-life of the product. Our products are sold in pharmacies and therefore have the same supply channel as medicinal products. A minimum of 24 months shelf life at 25C/60% RH is necessary, to guarantee a stable supply for pharmaceuticals and food supplements. Shelf life starts with preparation of bulk product and covers also the following elements: Storage at site (ca. 3 months as e.g. products are produced in batches and not continuously) Storage at warehouse of distributor (ca. 3 months) Storage at pharmacy Storage at consumer Due to this supply chain many pharmacies do not accept products (food supplements and medicinal products) with a shelf life of less than 12 months. To facilitate a constant supply of the market and to avoid unnecessary disposal of food supplements which cannot be supplied within shelf life, a shelf life of 24 months at 25C/60% RH must be met. References: 1 Formulation Challenges: Multiple Vitamin and Mineral Dosage Forms (Chapter 10) ByJoy A. Joseph BookPharmaceutical Dosage Forms - Tablets eBook ISBN9780429191152 2 Pharmaceutical Technology NOVEMBER 2000 Pharmaceutical Blister Packaging Rationale and Materials Ron Pilchik Kommentiert [AG1]: What is the unit here? Kommentiert [AG2R1]: Is there a source? 3