title: Processing difficulties and instability of carbohydrate microneedle arrays.
abstract: BACKGROUND
  A number of reports have suggested that many of the problems currently associated with the use of microneedle (MN) arrays for transdermal drug delivery could be addressed by using drug-loaded MN arrays prepared by moulding hot melts of carbohydrate materials.
  
  
  METHODS
  In this study, we explored the processing, handling, and storage of MN arrays prepared from galactose with a view to clinical application.
  
  
  RESULTS
  Galactose required a high processing temperature (160 degrees C), and molten galactose was difficult to work with. Substantial losses of the model drugs 5-aminolevulinic acid (ALA) and bovine serum albumin were incurred during processing. While relatively small forces caused significant reductions in MN height when applied to an aluminium block, this was not observed during their relatively facile insertion into heat-stripped epidermis. Drug release experiments using ALA-loaded MN arrays revealed that less than 0.05% of the total drug loading was released across a model silicone membrane. Similarly, only low amounts of ALA (approximately 0.13%) and undetectable amounts of bovine serum albumin were delivered when galactose arrays were combined with aqueous vehicles. Microscopic inspection of the membrane following release studies revealed that no holes could be observed in the membrane, indicating that the partially dissolved galactose sealed the MN-induced holes, thus limiting drug delivery. Indeed, depth penetration studies into excised porcine skin revealed that there was no significant increase in ALA delivery using galactose MN arrays, compared to control (P value < 0.05). Galactose MNs were unstable at ambient relative humidities and became adhesive.
  
  
  CONCLUSIONS
  The processing difficulties and instability encountered in this study are likely to preclude successful clinical application of carbohydrate MNs. The findings of this study are of particular importance to those in the pharmaceutical industry involved in the design and formulation of transdermal drug delivery systems based on dissolving MN arrays. It is hoped that we have illustrated conclusively the difficulties inherent in the processing and storage of carbohydrate-based dissolving MNs and that those in the industry will now follow alternative approaches.
authors: Medical Biology Centre, School of Pharmacy, Queen's University Belfast, Belfast, UK. r.donnelly@qub.ac.uk
authors: Ryan F
authors: RF
authors: Donnelly
authors: Desmond I J
authors: DI
authors: Morrow
authors: Thakur R R
authors: TR
authors: Singh
authors: Katarzyna
authors: K
authors: Migalska
authors: Paul A
authors: PA
authors: McCarron
authors: Conor
authors: C
authors: O'Mahony
authors: A David
authors: AD
authors: Woolfson
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002417:Cattle; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage; D005690:Galactose / Q000737:chemistry*; D006358:Hot Temperature; D006801:Humans; D006813:Humidity; D008567:Membranes, Artificial; D008845:Microinjections; D009339:Needles; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012828:Silicones / Q000737:chemistry; D012869:Skin Absorption; D013552:Swine; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D008567:Membranes, Artificial; D012828:Silicones; D012710:Serum Albumin, Bovine; D000622:Aminolevulinic Acid; D005690:Galactose