Influence of ageing on the gastrointestinal environment of the rat and its implications for drug delivery.
Age-mediated changes in gut physiology are considerations central to the elucidation of drug performance from oral formulations. Using rats of different age groups we measured the pH, buffer capacity, fluid volume, osmolality, and surface tension of gastrointestinal (GI) fluids, and therein explored the impact of these variables on prednisolone and mesalazine solubility in luminal fluids. We also studied the distribution of gut associated lymphoid tissue (GALT) and mucus layer thickness across the GI tract in rats of different age groups. At a mucosal level, there was an increase in GALT from young to adult rat. Gastrointestinal pH and buffer capacity remained mostly unchanged with age, except some pH differences in stomach and distal small intestine and a higher buffer capacity in the large intestinal fluids of young rats. Osmolality and surface tension also remained unaffected with the exception of a lower osmolality in elderly stomach and a lower surface tension in the small intestine of young rats. The difference in luminal environment on ageing influenced the solubility of studied drugs, for instance prednisolone solubility was shown to be higher in adult rats (mid small intestine and caecum) and solubility of mesalazine was significantly higher in the elderly distal small intestine.
Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Hamid A
HA
Merchant
Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Sarit C
SC
Rabbie
Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Felipe J O
FJ
Varum
Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Francisco
F
Afonso-Pereira
Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK. Electronic address: a.basit@ucl.ac.uk.
Abdul W
AW
Basit
D000375:Aging; D000818:Animals; D005750:Gastric Juice / Q000737:chemistry*; D041981:Gastrointestinal Tract / Q000033:anatomy & histology / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007419:Intestinal Secretions / Q000737:chemistry*; D008221:Lymphoid Tissue; D008297:Male; D019804:Mesalamine / Q000737:chemistry; D009093:Mucus / Q000737:chemistry; D009994:Osmolar Concentration; D011239:Prednisolone / Q000737:chemistry; D017208:Rats, Wistar; D012995:Solubility; D013500:Surface Tension; D014867:Water / Q000032:analysis
D014867:Water; D019804:Mesalamine; D011239:Prednisolone
Geriatrics; Laboratory animals; Mesalamine; Mesalamine (PubChem CID: 4075); Paediatrics; Personalised medicine; Pre-clinical studies; Prednisolone (PubChem CID: 5755)