title: Evaluating the sensitivity, reproducibility and flexibility of a method to test hard shell capsules intended for use in dry powder inhalers.
abstract: Pharmaceutical tests for hard shell capsules are designed for orally administered capsules. The use of capsules in dry powder inhalers is widespread and increasing and therefore more appropriate tests are required to ensure quality and determine if these capsules are fit for purpose. This study aims to determine the flexibility, reproducibility and sensitivity of a quantitative method that is designed to evaluate the puncture characteristics of different capsule shell formulations under different climatic conditions. A puncture testing method was used to generate force displacement curves for five capsule formulations that were stored and tested at two different temperatures (5°C and 19°C). Force-displacement puncture profiles were reproducible for individual capsule shell formulations. The methodology was able to discriminate between capsules produced using different primary materials i.e. gelatin versus hypromellose, as well as more minor changes to capsule formulation i.e. different material grades and excipients. Reduced temperature increased the forces required for capsule puncture however further work is required to confirm its significance. Results indicate the method provides a reproducible and sensitive means of evaluating capsule puncture. Future studies should validate the methodology at different test sites, using different operators and with different capsule shell formulations.
authors.affiliation: Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, United Kingdom.
authors.forename: Rosalind H E
authors.initials: RH
authors.lastname: Chong
authors.affiliation: Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, United Kingdom; Qualicaps Europe S.A.U., Alcobendas, Madrid, Spain.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Jones
authors.affiliation: Qualicaps Europe S.A.U., Alcobendas, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Díez
authors.affiliation: Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, United Kingdom.
authors.forename: James C
authors.initials: JC
authors.lastname: Birchall
authors.affiliation: Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, United Kingdom. Electronic address: coulmansa@cardiff.ac.uk.
authors.forename: Sion A
authors.initials: SA
authors.lastname: Coulman
mesh_terms: D002122:Calcium Chloride / Q000737:chemistry; D002214:Capsules / Q000737:chemistry*; D004356:Drug Storage; D058995:Dry Powder Inhalers; D005780:Gelatin / Q000737:chemistry; D006813:Humidity; D065347:Hypromellose Derivatives / Q000737:chemistry; D017616:Magnesium Compounds / Q000737:chemistry; D009566:Nitrates / Q000737:chemistry; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature
chemical_list: D002214:Capsules; D017616:Magnesium Compounds; D009566:Nitrates; D065347:Hypromellose Derivatives; C018330:magnesium nitrate; D005780:Gelatin; D002122:Calcium Chloride
keywords: Capsule; Dry powder inhaler; Gelatin; Hypromellose; Puncture; Quality Assurance