Particulate drug interactions with polymeric and elastomeric valve components in suspension formulations for metered dose inhalers.
OBJECTIVE
To characterise the adhesive interactions between three pulmonary active pharmaceutical ingredient (API) materials and the components of pressurised metered dose inhalers (pMDIs) obtained from two commercially available products (termed 'Prod-1' and 'Prod-2'). This is of potential interest, as a greater understanding of the interactions between specific APIs and surfaces may aid manufacturers in component selection during pMDI system development.


METHODS
The theoretical work of adhesion (DeltaG(132)) for each API-pMDI component interaction was calculated using the surface component analysis (SCA) approach. These results were correlated with corresponding API-pMDI component separation energy measurements determined using colloid probe AFM.


RESULTS
Strong correlations existed between separation energy and the DeltaG(132) parameters where the polar contribution was accounted for. This highlighted the adhesive influence of polar surface energy on each interaction in this study. Generally the largest adhesive interactions involved APIs and pMDI components which have a bipolar surface energy (i.e. both gamma(-) and gamma(+) >1 mJ m(-2)).


CONCLUSIONS
For each API-pMDI interaction in this study, the polar component of surface energy has the greater influence on adhesive events. The bipolar surface energetics of certain APIs and pMDI components were deemed responsible for the increased adhesive interactions observed with these materials. This study highlights that different materials can have different effects on the adhesive interactions with particulate APIs; information that could aid the manufacturer in producing more effective and efficient pMDI systems.
James
Jeff
J
Laboratory of Biophysics and Surface Analysis, School of Pharmacy, The University of Nottingham, Nottingham, UK. paxjj@nottingham.ac.uk
Davies
Martyn
M
Toon
Richard
R
Jinks
Phil
P
Roberts
Clive J
CJ
D000268:Adhesiveness; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry; D002116:Calcitonin / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D020724:Elastomers / Q000737:chemistry*; D036501:Metered Dose Inhalers; D018625:Microscopy, Atomic Force / Q000379:methods*; D000068656:Mometasone Furoate; D011108:Polymers / Q000737:chemistry*; D011244:Pregnadienediols / Q000008:administration & dosage / Q000737:chemistry; D013499:Surface Properties / Q000187:drug effects; D013535:Suspensions
D000336:Aerosols; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D020724:Elastomers; D011108:Polymers; D011244:Pregnadienediols; D013535:Suspensions; D000068656:Mometasone Furoate; C028815:salmon calcitonin; D002116:Calcitonin; D000420:Albuterol