COMPLEXATION WITH BETACYCLODEXTRINS IMPROVE STABILITY AND SOLUBILITY OF DRUGS IN DOSAGE FORMS قحطان جاسم حسون

Cyclodextrins (CDs) are cyclic oligosaccharides obtained from starch by enzymatic cyclisation using enzymes called cycloglycosyl transferases

Types of cyclodextrins (related to No.of unhydrousglucose unites); ALPHA-cyclodextrin (6 units ) BETA-cyclodextrin (7 units ) GAMMA-cyclodextrin (8 units) However so far only betacyclodextrin has a significant industrial usage.

Betacyclodextrin are bound by alpha-1,4 glycosidic bonds, give (7 cyclo-a(1,4)-anhydroglucose units.

Derivatives of cyclodextrins. HPBCD :2- HydroxyPropyl BetaCycloDextrin RAMEB :Randomly Methylated Betacyclodextrin DIMEB : 2,6-dimethyl-betacyclodextrin HPBCD has an ideal profile for pharmaceutical applications

The hydrophobic cavity formed by Betacycodextrin ring can accommodate the guest molecule and form complex or inclusion compound.

Beta cyclodextrin is used to prepare encapsulated drug,by slurry method followed by drying Hydroxy Propyl Betacyclodextrin HPBCD is used for parenteral solution Safe, pyrogen free and non toxic

Preparation of diclofenac sodium ampoule ;75mg/3ml Diclophenac sod. Sod.metabisulfite 0.1% EDTA 0.05% Benzyl alcohol 7% amber glass container

Formulation with HPBCD Diclophenac sod. 2.5% Sod.metabisulfite 0.1% EDTA 0.05% Benzyl alcohol 2% HPBCD 1.25% N2 bubbling pH 7.8 Membrane filtration (0.22 µm) Amber glass ampoule (grade No.1)

Stability Study by storing ampoules at 40°C & 75% RH for 6 months

Stability on storage at 40°C & 75% RH Commercial formula 6 th month 3 rd month 1st month initialTest yellow==slightly yellow color ===Nil particles pH 99.2%99.6%100%101%Assay free pyrogen ===NilMT New formula with CD 6 th month 3 rd month 1 st month initialtest ===colorlesscolor ===Nil particles pH 99.8%100% 100.1%Assay ===free pyrogen ===NilMT

Assay by HPLC 70% methanol in phosphate buffer pH 2.5, column C8, at 254 nm, Rt = 10 minutes

Pyrogen test

Pharmaceutical chemistry and industry