Stability Evaluation of Two Non-Synthetic for Use in Fully Formulated Film Coating Systems Charles Cunningham, Chris Neely and Thomas P. Farrell Colorcon Inc., Global Headquarters, 275 Ruth Road, Harleysville, PA 19438 USA; www.colorcon.com/about/contact

Purpose Results

There is an increasing interest in the use of non-synthetic pigments in film coating formulations Formulated Powder Stability – Carmine Figure 3. Change of Formulated Powders Containing Beta Carotene (40°C / 75% RH) Figure 6. Color Change of Coated Tablets with Purple Carmine (30°C / 65% RH) The coated tablets with beta carotene exhibited poor color stability at both storage con- for dietary supplements and pharmaceuticals. Since non-synthetic pigments are typically The specification limit for color change was NMT 3.5 ΔE for the formulations containing purple ditions. Significant fading of the tablets was observed visually and instrumentally. Although the derived from natural sources, color variability and color stability in formulated coating systems is 30 4.0 tablet samples were stored in the dark, beta carotene is prone to oxidation induced decomposi- carmine. After 6 months storage at 40°C / 75% RH, none of the coating systems containing Specification a concern. In addition to assessing the stability of the pigment on the coated tablet, it is also 3.5 tion as well as sensitivity.1 Prior to the use of this pigment in film coating applications, fur- purple carmine exceeded 2.5 ΔE in color difference. (Figure 1). Samples stored for 6 months 25 Limit E) necessary to examine the color stability of the pigments in the pre-formulated coating material E) 3.0 ther studies should be conducted to determine optimum packaging and storage conditions that ȴ at 30°C / 65% RH did not exceed 1.6 ΔE (Figure 2). ȴ ( (   20 in order to ensure reproducible color over a potentially extended material storage period. The 2.5 would reduce the potential for color change. purpose of this study was to evaluate the color stability of two non-synthetic pigments in model 2.0 pre-formulated film coating systems under accelerated storage conditions. 15 Opadry Opadry difference difference   1.5 10 OpadryII OpadryII

Color 1.0 Figure 1. Color Change of Formulated Powders Containing Purple Carmine (40°C / 75% RH) Color OpadryNS OpadryNS 5 Specification 0.5 4.0 Limit Conclusions Methods 0 0.0 Specification 3.5 Limit Purple carmine and beta carotene pigments were formulated into three coating systems at a 7% 1.5 3.0 4.5 6.0 Initial 1.0 2.0 3.0 The non-synthetic pigments evaluated in this study differed significantly in their stability under

E) 3.0

ȴ accelerated storage conditions. In addition to storage conditions, formulation of the film coating ( Months Months

w/w usage level. (Table 1).  2.5 base also affected stability. The stability of non-synthetic pigments in film coating systems must 2.0 Opadry be carefully evaluated in order to determine proper product shelf life and appropriate packaging Figure 4. Color Change of Formulated Powders Containing Beta Carotene (30°C / 65% RH)

difference and storage conditions. As a result of this study, the purple carmine pigment was successfully  1.5 OpadryII The tablets with purple carmine pigment exhibited good stability in either storage condition Table 1. Materials Used in the Study 30 qualified for use in fully formulated film coating systems and complemented previously

Color 1.0 irrespective of formulation type. These results provide confidence that this pigment would be OpadryNS qualified non-synthetic pigments (Figure 9). Studies are continuing on additional non- 0.5 stable in the intended end use film coating application. Coating Formulations (Colorcon Inc. West Point, PA) Polymer Base 25 synthetic pigments. E)

0.0 ȴ Coated Tablet Stability – Beta Carotene ( ®  20 Opadry, Complete Film Coating System Hypromellose 1.5 3.0 4.5 6.0 The specification limit for color change was NMT 3.0 ΔE for the coated tablets containing beta Months 15 Opadry II,® High Performance Film Coating System Polyvinyl alcohol Opadry carotene. After just 1-month storage at either 40°C / 75% RH or 30°C / 65% RH, all coated difference  tablets failed the color change specification (Figures 7 and 8). 10 OpadryII Figure 9. Examples of Coated Tablets Employing Stable Non-synthetic Pigments Including Opadry® NS, Complete Film Coating System for Nutritional Supplements Cellulosics Color OpadryNS Purple Carmine 5 Specification Limit Pigments (CHR Hansen, Milwaukee, WI) Color Figure 2. Color Change of Formulated Powders Containing Purple Carmine (30°C / 65% RH) 0 Figure 7. Color Change of Coated Tablets with Beta Carotene (40°C / 75% RH) 1.5 3.0 4.5 6.0 Purple carmine CC-5000-L-P-B Purple 4.0 Months 18 3.5 Specification Beta carotene BC-100Y-WSP Bright Limit E) 15 E) 3.0 ȴ ȴ ( ( The beta carotene pigment exhibited poor color stability at the 40°C / 75% RH storage   2.5 condition. At 30°C / 65% RH, the results were significantly better, but showed that the color 12 2.0 Opadry stability could be formulation dependent. This pigment could be qualified for use in some types 9 Opadry difference  difference The coating formulations (1kg) were packaged in fiber cartons with sealed polyethylene liners and  1.5 OpadryII of coating formulations, but longer term stability studies would need to be conducted to further OpadryII assess product shelf life and proper storage conditions. 6 Color OpadryNS stored in the dark at 30°C / 65% RH and 40°C / 75% RH for 6 months. At 1.5 month intervals, Color 1.0 OpadryNS samples of the stored film coating formulations were reconstituted in deionized water (Di H2O) and 3 Specification 0.5 Coated Tablet Stability – Purple Carmine Limit applied to Lanetta cards using a Bird Film Applicator (150 µm). The cards were dried in a 50°C 0.0 The specification limit for color change was NMT 3.5 ΔE for the coated tablets containing purple 0 oven for 10 minutes then measured for color change. 1.5 3.0 6.0 carmine. After 3-months storage at 40°C / 75% RH, none of the coated tablets exceeded 1.5 Initial 1.0 2.0 3.0 Each coating formulation was also applied on 350 mg placebo tablets (to a 3.0% weight gain) , in a Months ΔE in color difference. (Figure 5). Coated tablets stored for 3 months at 30°C / 65% RH did Months 12” fully-perforated pan (Labcoat I, O’Hara Technologies). The coated tablets were packaged in foil- not exceed 1.0 ΔE (Figure 6). sealed 100 cc HDPE bottles (50 tablets per bottle) and stored in the dark at 30°C / 65% RH and 40°C / 75% RH for three months. The coated tablets were measured monthly for color change. Figure 5. Color Change of Coated Tablets with Purple Carmine (40°C / 75% RH) Figure 8. Color Change of Coated Tablets with Beta Carotene (30°C / 65% RH) Both the powder and coated tablet samples were tested for color change using a Datacolor 600 The purple carmine pigment exhibited good stability in either storage condition irrespective of spectrophotometer (Datacolor, Lawrenceville, NJ) employing the Commission Internationale de formulation type. These results indicated that coating formulations containing this pigment will 4.0 Specification 18 3.5 l’Eclairage (CIE) L* a* b* system. The total color difference (ΔE) from the target reference color remain within specification for up to 2 years. Limit

was determined by calculating the distance between two points in the using the E) 15 E) 3.0 ȴ ȴ (

Formulated Powder Stability – Beta Carotene (  following equation:  2.5 12 References The beta carotene pigmented formulations exhibited significant color change and all exceeded the 2.0 specification (3.0 ΔE) after 3 months storage at 40°C / 75% RH (Figure 3). After 6 months at Opadry 9 Opadry 1. H. Morais P. Rodrigues C. Ramos E. Forgács T. Cserháti J. Oliveira; Effect of ascorbic acid on the stability of β–carotene difference  difference 30°C / 65% RH storage conditions, the beta carotene formulations were visually comparable to the  1.5 OpadryII OpadryII and capsanthin in paprika (Capsicum annuum) powder, Nahrung / Food Research, Volume 46, Issue 5, 1 September 6 2002, Pages: 308–310.

Color OpadryNS 2 2 2 1/2 reference but only the Opadry NS formulation met the instrumental color change specification with Color 1.0 OpadryNS ƩE* = [(L*1 – L*2) + (a*1 – a*2) + (b*1 – b*2) ] a 0.8 ΔE (Figure 4). 3 Specification 0.5 Limit 0.0 0 Initial 1.0 2.0 3.0 Initial 1.0 2.0 3.0 All trademarks, except where noted, are property of BPSI Holdings LLC. The information contained in this document is proprietary to Colorcon, Inc. and may not be used or disseminated inappropriately. Months Months ©BPSI Holdings LLC. 2010 This document is valid at the time of distribution. Distributed 30-Sep-2021 (UTC) Powered by TCPDF (www.tcpdf.org)