Dexamethasone eye drops based on the products of its interaction with 2-hydroxypropyl-β-cyclodextrin: Synthesis and study

Abstract

Corticosteroids, especially dexamethasone (DM), play an important role in eye therapy [I]. DM is used in the form of a 0.1% suspension or 0.05-0.1% solutions. Although DM is now produced in Russia, no domestic ophthalmologic preparations have been developed until recently.The purpose of this work was to prepare DM-based eye drops using the commercially available parent compound and domestic auxiliary substances. In particular, for DM dissolution we used 2-hydroxypropyl-13-cyclodextrin (HPCD) known to form inclusion complexes with steroidal compounds [2]. EXPERIMENTAL CHEMICAL PARTCDM, mote/liter 0.07The experiments were performed with DM obtained from the Akrikhin chemico-pharmaceutical plant (Akrikhin jointstock company) and HPCD (Novodeks Ltd., Ufa) produced according to State Technical Conditions TU 406K-H2100-002 -92 with 3.7 hydroxyl groups per macrocycle.The effect of HPCD on DM solubility was studied using a series of HPCD solutions with concentrations ranging from 5 to 100 mg/ml at a 5 mg/ml step.To 100 ml of an HPCD solution was added 50 mg DM and the mixture was treated in a shaker for 1 rain and allowed to stand for 1 day, after which the DM content in the supernatant liquid was determined by spectrophotometry at L = 246 nm (~ = 440). Figure 1 shows the results of averaging over three parallel determinations. As seen from these data, the solubility of DM in a 100mg/ml HPCD solution increases by a factor of 170 compared to the DM solubility in water. The dependence of the DM solubility on the HPCD concentration in water belongs to the type A [3], which is evidence of the DM-HPCD interaction with the formation of a water-soluble complex. No deviations from the linear de-State Pharmaceutical Academy, Pyatigorsk, Russia. pendence were observed in the entire HPCD concentration range studied (type AL ), which is indicative of considerable HPCD solubilization and the high solubility of the HPCD-DM compound formed.These results indicate that HPCD can be used for the preparation of DM solutions, the optimum HPCD concentration being 4%. Because the DM solutions are intended for use in ophthalmology, there arises an important question concerning the stability of both DM and HPCD in solution. To our knowledge, no data were reported on HPCD stability in aqueous solutions. For this reason, we have studied the be-160 0.06 0.05 0.04 0.03 0.02 0.0l 0. '02 0104 0106

Pharmaceutical applications of cyclodextrins: effects on drug permeation through biological membranes

“…Acetazolamide HPbCD [72][73][74] Anandamides HPbCD [75,76] Cannabinoids (various) HPbCD [77] Ciclosporin aCD [78][79][80] Dehydroepiandrosterone HPbCD [81] Dexamethasone HPbCD, gCD [82][83][84][85][86][87][88] Diclofenac HPbCD, RMbCD [89] Dipivefrine SBEbCD [90] Disulfiram HPbCD [91,92] Dorzolamide RMbCD, gCD [88,93] Enalaprilat HPbCD [94] Enalapril maleate HPbCD [94] Ethoxyzolamide HPbCD [72] Fluorometholone HPgCD [95] Hydrocortisone HPbCD [96,97] Ketoconazole HPbCD [98] Loteprednol etabonate HPbCD, DMbCD [99] Pilocarpine aCD, bCD, HEbCD, HPbCD, SBEbCD [100][101][102][103] Prostaglandins HPbCD [104] Rufloxacin HPbCD [105] Thalidomide HPbCD [106] D 9 -Tetrahydrocannobinol aCD [107,108] Nasal drug delivery: Acyclovir HPbCD [115] 17b-Estradiol DMbCD [116] Insulin aCD, DNaCD, HPaCD, bCD, DMbCD, HPbCD [117] Midazolam SBEbCD [118,…”

Microspheres and nanotechnology for drug delivery

“…Thus, through cyclodextrin complexation it has been possible to formulate lipophilic water-insoluble steroids as aqueous eye drop solutions. 13,[35][36][37][38][39][40] Once included in the cyclodextrin cavity, the drug molecules may be dissociated from the cyclodextrin molecules through complex dilution in the aqueous tear fluid. Since no covalent bonds are formed or broken during the guest-host complex formation, the complexes are in dynamic equilibrium with free drug and cyclodextrin molecules.…”