Drug Formulations

Beyond the already discussed stabilising effects, cyclodextrins reduce the reactivity of drugs in the solid state, enhance their dissolution rate and solubility, and reduce the bad mouth taste. They can also convert sticky lipids, liquids or even gaseous substances to crystalline solids, which can be easily mixed and tabletted. The cyclodextrin complexes are always fine microcrystalline powders, irrespective of the method of preparation.

Incompatibility
A frequent problem in a multicomponent system is incompatibility. Molecularly encapsulated drugs do not interact with other substances and additives within the same product. Papaverine hydrochloride and phenobarbital sodium are incompatible, because of the formation of insoluble bases. Complexing the phenobarbital with b-cyclodextrin, it becomes compatible with apaverine hydrochloride. The menadione content of premixes is protected when complexed with b-cyclodextrin complex.

Polymorphism
There are drugs, which have different crystal structures, with different physical properties, including different solubilities. The bioavailability of the same chemical entity might therefore be very different, depending on its crystal structure. Interconversion of these structures can occur in tablets. Complexing spironolactone with g- cyclodextrin the dissolution acid bioavailability properties can be maintained for a longer duration..

Sustained release
Complexation of a drug with cyclodextrins generally results in an accelerated disssolution, and absorption. Frequently however, a sustained release is required. The enhanced bioavailability results in an enhanced blood level with enhanced, often, longer lasting biological effect. A sustained release effect with cyclodextrins is possible. For example butamben cyclodextrin through a silicone membrane.. Another method to attain a sustained release is to prepare a mixed cyclodextrin complex of a drug e.g. indomethacin, theophyllin, or acetaminophen, and of a fatty acid glyceride. The aqueous suspension of the components is spray-dried, and encapsulated. The local anaesthetic effect of prilocaine or lidocaine can be elongated with b-cyclodextrin or dimethyl-b-Cyclodextrin

Liquid-to-solid conversion
Cyclodextrin complexes of complexable liquids are microcrystalline, easily tablettable powders with a good storage life, e.g. clofibrate ,benzaldehyde zyxorin, menthol, garlic oil ,nitroglycerin etc. Mixing amylase with a granulated complex before tabletting, the intestinal absorption will be even faster.

Improvement of physical properties of tablets
Cyclodextrins are not hygroscopic, therefore mixing them with hygroscopic drugs, the deliquescence of the composition is reduced. For eg. the formulation of sodium valproate.
The freeze dried phenytoin-b-cyclodextrin (10% solid) formed a stable suspension in a 50:50 water: glycerin mixture without any other additive. The b-cyclodextrin complex of hydrogen chloride is more suitable for the colour stabilisation of Probon tablets then betaine hydrochloride.

Dermal and nasal preparation (ointments, creams, sprays)
In a b-cyclodexrin complex of hydrocortisone or triamcinolone-acetonide, the dissolution is increased manifold. The dissolution of sulfacetomide sodium from an, eye ointment containing its b-cyclodextrin in complex (2% w/w sulfacetamide), is also enhanced considerably. Similarly is the case of in vitro release of betamethasone from gel and hydrophilic ointments. The improved antimicrobial activity of an antiseptic cream (containing dequalinium chloride) after adding b-cyclodextrin can be explained by the enhanced solubility of the drug. Adhesive tapes or bandages for topical application with sustained drug release are increasing in popularity. The trans dermal absorption and stability is better when the drug is cyclodextrin complexed. For eg. a-or b-cyclodextrin complexes of nitroglycerin methyl-salicylate.nonylic acid vanillin aldehyde , tocopherol acetate ,tri-amcinolone acetonide etc. A silver alkanolamine b-cyclodextrin complex was reported to be useful for the local treatment of wounds and infections. The absorption of insulin from a nasal spray considerably improves from an a-cyclodextrin containing spray.

Suppositories
Mixing certain drugs and essential oil to suppositorial bases will result in a decrease of the melting point, break strength, and sometimes stability (shelf life) of the prepared suppositories.
The dissolution of fennel oil from fat based suppositories and for indomethacin improves considerably after complexing with b-cyclodextrin. Similar results were reported on rectal absorption of cyclodextrin complexed flurbiprofen, phenobarbital acetohexamide and 16,16-dimethyl-trans-D2-PGE,-methylester, oil from Witepsol suppository base.

Eye-drops, ointments
Generally the application of cyclodextrins in ophthalmological preparations (eye drops and ointments), improves the stability and solubility of the drug, and strongly reduces its eye-irritating effect. The preparation of cyclodextrin containing eye-drops is reported with various drugs: indomethacin, flurbiprofen , diclofenac Na , lysozym , steroids etc.Lidocaine base, the water soluble HCI salt of which is used as a local anaesthetics, is poorly soluble in water. It is however readily dissolved in aqueous dimethyl-b-cyclodextrin (DlMEB) solution.

Injections
This may be to enhance the solubility of poorly soluble drugs e.g. Prostaglandin-E, and cyclohexyl-anthranylate, or to reduce their local irritating effect e.g. flurbiprofen and tiamulin . On the other hand the administered dose of b-cyclo- dextrin has to be kept low, For the reduction of local irritation g-cyclodextrin is used in injections. Injectable aqueous solutions can be prepared from b-cyclodextrin complexed ergocalciferol in presence of polyols or sugars. Thiopental forms a 1: 1 complex with g-cyclodextrin, which is more stable than thiopental Na at 40oC and 75% relative humidity. It is very soluble, and injectable solutions may be prepared. The haemolytic activity of analgesic benzyl alcohol injections can beprevented by a-, b- or g-cyclodextrin (2.5% benzylalcohol + 2% a-cyclodextrin in physiological saline. Cholic acids are poorly soluble but have a haemolytic activity. injectable preparations can be prepared with b-cyclodextrin.

Inhalants
Volatile oils are widely used for inhalation therapy with hot vapours. The volatile components form stable complexes with b-cyclodextrin.