title: Discomfort from an alkaline formulation delivered subcutaneously in humans: albumin at pH 7 versus pH 10.
abstract: OBJECTIVE
  There is a paucity of data regarding tolerability of alkaline drugs administered subcutaneously. The aim of this study was to assess the tolerability of alkaline preparations of human albumin delivered subcutaneously to healthy humans.
  
  
  METHODS
  We compared the tolerability of neutral versus alkaline (pH 10) formulations of human albumin in ten volunteers. With an intent to minimize the time required to reach physiological pH after injection, the alkaline formulation was buffered with a low concentration of glycine (20 mmol/L). Each formulation was given at two rates: over 5 seconds and over 60 seconds. A six-point scale was used to assess discomfort.
  
  
  RESULTS
  For slow injections, there was a significant difference between pH 7.4 and pH 10 injections (0.4 ± 0.2 vs 1.1 ± 0.2, mean ± SEM; p = 0.025), though the degree of discomfort at pH 10 injections was only 'mild or slight'. For fast injections, the difference between neutral and alkaline formulations was of borderline significance. Inflammation and oedema, as judged by a physician, were very minimal for all injections, irrespective of pH.
  
  
  CONCLUSIONS
  For subcutaneous drug administration (especially when delivered slowly), there was more discomfort associated with alkaline versus neutral formulations of albumin, though the discomfort was mild. This study suggests that there is little discomfort and inflammation resulting from subcutaneous administration of protein drugs formulated with weak buffers at alkaline pH.
authors.affiliation: Legacy Health and Legacy Research Institute, Portland, OR, USA. kenward503@msn.com
authors.forename: W Kenneth
authors.initials: WK
authors.lastname: Ward
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Castle
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Branigan
authors.forename: Ryan G
authors.initials: RG
authors.lastname: Massoud
authors.forename: Joseph
authors.initials: J
authors.lastname: El Youssef
mesh_terms: D000328:Adult; D000418:Albumins / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D002021:Buffers; D002626:Chemistry, Pharmaceutical; D004311:Double-Blind Method; D004487:Edema / Q000209:etiology; D004890:Erythema / Q000209:etiology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000209:etiology; D007279:Injections, Subcutaneous / Q000009:adverse effects; D008297:Male; D009922:Oregon; D010146:Pain / Q000175:diagnosis / Q000209:etiology; D010147:Pain Measurement; D013997:Time Factors
chemical_list: D000418:Albumins; D002021:Buffers