Gastrointestinal mucoadhesive patch system (GI-MAPS) for oral administration of G-CSF, a model protein

A new gastrointestinal mucoadhesive patch system (GI-MAPS) has been designe d for the oral delivery of protein drugs. The system consists of four layer ed films, 3.0 x 3.0 mm(2), contained in an enteric capsule. The 40 mum back ing laver is made of a water-insoluble polymer, ethyl cellulose (EC). The s urface layer is made of an enteric pH-sensitive polymer such as hydroxyprop ylmethylcellulose phthalate (HP-55 (R)), Eudragit (R) L100 or S100 and was coated with an adhesive layer. The middle laver, drug-containing layer made of cellulose membrane is attached to the EC backing layer by a heating pre ss method. Both drug and pharmaceutical additives including an organic acid , citric acid, and a non-ionic surfactant, polyoxyethylated castor oil deri vative (HCO-60 (C)), were formulated in the middle layer. The surface layer was attached to the middle layer by an adhesive layer made of carboxyvinyl polymer (Hiviswako (R) 103). Fluorescein (FL), 30 mg, was first used as a model drug for oral administration of GI-MAPS having different surface laye rs in beagle dogs. The plasma FL concentration vs. time profiles demonstrat ed that the targeting of the systems was obtained. because the T-max, the t ime when plasma FL concentrations reaches to its maximum lelev, was 2.33 +/ - 0.82 h for HP-55 system, 3.33 +/- 0.41 h for Eudragit L100 system and 5.0 0 +/- 0.00 h for Eudragit S100 system. The same three kinds of GI-MAPSs con taining 125 mug of recombinant human granulocyte colony-stimulating factor (G-CSF) were prepared and orally administered to dogs and the increase in t otal white blood cell (WBC) counts were measured as the pharmacological ind ex for G-CSF. Comparison with the total increase of WBCs after iv injection of the same amount of G-CSF (125 pg) indicated the pharmacological availab ilities (PA) of G-CSF were 23%, 5.5% and 6.0% for Eudragit L100, HP-55 and Eudragit S100 systems. By decreasing the amount of HCO-60 and citric acid, the PA of G-CSF decreased. These results suggest the usefulness of GI-MAPS for the oral administration of proteins. (C) 2001 Elsevier Science Ltd. All rights reserved.