(W1230-09-59) Application of Novel Partially Pregelatinized Cassava [tapioca] Starch as Substitute Filler-Diluent to Lactose in Personalized Substance-Abuse Therapy for Lactose Intolerant Population

Purpose: A study protocol was developed to evaluate partially pregelatinized cassava [tapioca] starch as a possible substitute to lactose as a filler-diluent in personalized substance-abuse therapy for lactose intolerant population

Methods: Prototype formulations containing naltrexone HCl (1%w/w), a blocker of the mu-opioid receptor (Naltrexone HCl, USP, Medisca, Montreal, Canada), were compounded using lactose monohydrate (99%w/w) as filler-diluent (Lactose, NF [Monohydrate], Medisca, Canada) and partially pregelatinized cassava [tapioca] starch (99%w/w) as filler-diluent (Cassava Starch 2060GG, Cassava Pharma, NY), respectively. Each formulation was filled into capsules with target weight of 270 mg (Capsule Coni-Snap #3, Medisca, Canada), using capsule filler (Profiller 1100, Medisca, Canada). The capsules were analyzed using USP < 2091 > (Weight Variation) and USP < 701 > (Disintegration). Further analysis was conducted based on Student T-test (Minitab Statistical Software 22, Minitab, IL).

Results: It was found that the Naltrexone HCl-based formulations using lactose monohydrate as filler-diluent (Batch A) and partially pregelatinized cassava [tapioca] starch as filler-diluent (Batch B), conformed to USP < 2091 > Weight Variation, with none of the capsules exhibiting any variation outside 7.5% acceptance criteria (Table 1). The results also showed that all six (6) capsules in each formulation as subjected to the USP ( < 701 > Disintegration analysis, met the acceptance criteria with disintegration times less than 5 minutes (Figure 1). Results from the Process Capability (CpK) analysis showed that both formulations demonstrated acceptable CpK values > 1.00 (Batch A was 1.05; Batch B was 1.16) [Figure 2a], an indication of stability in the encapsulation process and methodology. Furthermore, statistical estimation of difference conducted using Two-Sample Student T-test showed no significant difference between the two groups (p-value: 0.005), with pooled standard deviation (8.31) and acceptable difference at 95% CI (2,27, 6.92). There was, however, slight wider variance in the data spread within the Lactose-based sample group (Batch A) when compared to Tapioca-based sample group (Batch B), as shown by the individual value plot (Figure 2b). Future work will attempt to fully characterize such within-group variance observed.

Conclusion: The study shows that partially pregelatinized cassava [tapioca] starch possesses qualities and attributes as a potential substitute filler-diluent to lactose in personalized substance-abuse therapy for lactose intolerant population.

References: 1. World Population Review; https://worldpopulationreview.com/country-rankings/lactose.
2. Gerald A. Hebbink, Bastiaan H.J. Dickhoff: Lactose - Evolutionary Role, Health Effects, and Applications; 2019, Pages 175-229; https://doi.org/10.1016/B978-0-12-811720-0.00005-2.
3. USP-NF Disintegration (General Chapter).
4. USP Weight Variation of Dietary Supplements (General Chapter).

Acknowledgements: The authors acknowledge the support of University of Cyprus and UPP Pharmaceutical USA for all their assistance during this research study.

Table 1: Comparing Weight Variation in Prototype Capsule Formulations using USP <2091>;
Figure 1: Comparing Capsule Disintegration from Prototype Formulations (USP <701>), (N=6)


Figure 2a: Process Capability Analysis based on Capsule Loading Efficiency;
Figure 2b: Analysis of Weight Variation based on Individual Value Plots

Figure 3a: Photos of encapsulated Samples from Batch A and Batch B;
Figure 3b: Global Lactose Intolerance (% of Population)