Bary A R, Tucker I G, Davies N M
Formulation and Drug Delivery Group, School of Pharmacy, University of Otago, Dunedin, New Zealand.
Eur J Pharm Biopharm. 2000 Sep;50(2):237-44. doi: 10.1016/s0939-6411(00)00108-9.
The in vivo ocular bioavailability of hydrocortisone (HC) in the NZW rabbit was determined following topical administration of solutions containing HC (1%) with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) alone, or containing the mucoadhesive, viscosity enhancing polymers sodium hyaluronate (0.2 and 0.5% w/v) or Carbopol 934P (0.1% w/v). A 1% HC suspension was used as control. Formulation of HC as a solution with HP-beta-CD in the absence of polymer increased the bioavailability of HC in the aqueous humour by approximately 55% and cornea by 75% when compared to suspension. Inclusion of either polymer did not result in any further increase in ocular bioavailability over that noted for the polymer-free solution. The in vitro corneal permeability of HC was also evaluated. A linear relationship (r(2)=0.999) was noted between corneal permeability and the concentration of free (uncomplexed) HC in solution. Permeability was greatest when formulated either as a suspension, or as an HP-beta-CD solution in which the concentration of free (uncomplexed) HC is equivalent to that of a saturated solution. Thus, when using cyclodextrins in the reformulation of ophthalmic suspensions as solutions, consideration must be given to the concentration of cyclodextrin used and to the benefits of including viscosity enhancing polymers.
在新西兰白兔体内，分别局部给予含1%氢化可的松（HC）与羟丙基-β-环糊精（HP-β-CD）的溶液、含粘膜粘附性增稠聚合物透明质酸钠（0.2%和0.5% w/v）或卡波姆934P（0.1% w/v）的1% HC溶液，测定HC的眼内生物利用度。以1% HC混悬液作为对照。与混悬液相比，在无聚合物存在时将HC与HP-β-CD配制成溶液，可使房水中HC的生物利用度提高约55%，角膜中提高75%。加入任何一种聚合物均未使眼内生物利用度比无聚合物溶液有进一步提高。还评估了HC的体外角膜渗透性。观察到角膜渗透性与溶液中游离（未络合）HC浓度之间呈线性关系（r(2)=0.999）。当配制成混悬液或游离（未络合）HC浓度与饱和溶液相当的HP-β-CD溶液时，渗透性最大。因此，在将眼科混悬液重新配制成溶液时使用环糊精时，必须考虑所用环糊精的浓度以及加入增稠聚合物的益处。
