Drug-carrier binding and enzymatic carrier digestion in amorphous solid dispersions containing proteins as carrier.
In order to further explain the ability of gelatin 50PS and bovine serum albumin (BSA) to generate supersaturation of a series of poorly soluble drugs (carbamazepine, cinnarizine, diazepam, itraconazole, nifedipine, indomethacin, darunavir (ethanolate), ritonavir, fenofibrate, griseofulvin, ketoconazole, naproxen, phenylbutazone and phenytoin), drug-polymer binding was investigated using solution NMR and equilibrium dialysis experiments. Binding characteristics of the biopolymers were compared to those of PVP, PVPVA and HPMC. Since both biopolymers are prone to enzymatic digestion, we evaluated the influence of proteolytic enzymes like pepsin and pancreatin on the dissolution properties of poorly soluble compounds when formulated as amorphous solid dispersions with gelatin 50PS and BSA. Evidence is being presented that supports the importance of drug-polymer binding in inducing and stabilizing supersaturation of poorly soluble drugs and enhancing dissolution from ASDs. In fact, BSA displayed drug binding with nearly all tested model drugs while in case of gelatin 50PS binding was observed for 5 out of 12 drugs. Addition of pepsin or pancreatin during dissolution of the biopolymer-containing ASDs leads to a drop in the concentration of the drug pointing to enzymatic digestion of the gelatin and BSA. However, after digestion, these formulations still outperformed their crystalline counterparts.
['Pas|Timothy|T|', 'Bergonzi|Alessandra|A|', 'Lescrinier|Eveline|E|', 'Vergauwen|Bjorn|B|', 'Van den Mooter|Guy|G|']
D004337:Drug Carriers D065546:Drug Liberation D005780:Gelatin D010194:Pancreatin D010434:Pepsin A D004364:Pharmaceutical Preparations D012710:Serum Albumin, Bovine
Amorphous solid dispersions Gelatin Bovine serum albumin (BSA) Supersaturation Drug-polymer binding Biopolymer(s) Carbamazepine (PubChem CID: 2554) Cinnarizine (PubChem CID: 1547484) Darunavir Ethanolate (PubChem CID: 23725083) Diazepam (PubChem CID: 3016) Fenofibrate (PubChem CID: 3339) Griseofulvin (PubChem CID: 441140) Indomethacin (PubChem CID: 3715) Itraconazole (PubChem CID: 55283) Phenylbutazone (PubChem CID: 4781) Phenytoin (PubChem CID: 1775) Ritonavir (pubchem CID:392622) ketoconazole (PubChem CID: 456201) naproxen (PubChem CID: 156391) nifedipine (PubChem CID: 4485)