Design of innovated lipid-based floating beads loaded with an antispasmodic drug: in-vitro and in-vivo evaluation.
BACKGROUND
Drotaverine hydrochloride (DRT) is used to treat gastrointestinal spasms accompanied with diarrhoea. Hence, the drug suffers from brief residence in the highly moving intestine during diarrhoea which leads to poor bioavailability and frequent dosing.


OBJECTIVE
This study aimed to extend DRT residence in the stomach.


METHODS
Calcium alginate floating beads were prepared using sodium alginate, isopropylmyristate (oil), and Gelucire® 43/01 (lipid) adopting emulsion gelation technique. The beads were evaluated for their floating ability, DRT entrapment efficiency and in-vitro release. Gelucire® 43/01 /oil-based beads of the selected formula were coated using ethylcellulose and different plasticizers as polyethylene glycol 400 and triethyl citrate to retard the drug release. The coated beads were re-characterized. Finally, the best formulae were investigated for their in-vivo floating ability in dogs besides their delivery to the systemic circulation compared to drug powder in human volunteers.


RESULTS
Incorporation of Gelucire® 43/01 to oil-based beads enhanced the in-vitro performance of the beads. Coated beads prepared using drug:sodium alginate ratio of 1:3 (w/w), 20% (w/v) isopropylmyristate, 20% (w/v) Gelucire® 43/01 showed promising in-vitro performance. The beads floated for 12 h in the dogs' stomach and produced three-fold increase of the total amount of DRT absorbed within 24 h compared to that of DRT powder.


CONCLUSIONS
Gelucire® 43/01 /isopropylmyristate-based calcium alginate floating beads coated with ethylcellulose using either PEG 400 or TEC as plasticizers proved to be a successful dosage form in extending DRT release.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University , Cairo , Egypt.
Sally
S
Adel
Nermeen Adel
NA
ElKasabgy
D000328:Adult; D000464:Alginates / Q000737:chemistry; D000818:Animals; D003967:Diarrhea / Q000188:drug therapy; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000138:chemical synthesis*; D008747:Methylcellulose / Q000031:analogs & derivatives; D009226:Myristates / Q000737:chemistry; D010208:Papaverine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010276:Parasympatholytics / Q000008:administration & dosage*; D004364:Pharmaceutical Preparations; D014280:Triglycerides / Q000737:chemistry
D000464:Alginates; D004655:Emulsions; D006603:Hexuronic Acids; D008081:Liposomes; D009226:Myristates; D010276:Parasympatholytics; D004364:Pharmaceutical Preparations; D014280:Triglycerides; C507309:gelucire 43-01; C008205:isopropyl myristate; D020723:Glucuronic Acid; D008747:Methylcellulose; C005317:drotaverin; D010208:Papaverine
Drotaverine hydrochloride; glass transition temperature; isopropylmyristate; pharmacokinetics