Antimicrobial Preservatives in Cyclodextrin-Containing Drug Formulations.

In general, antimicrobial preservatives are essential components of multidose pharmaceutical formulations to prevent microbial growth and contamination, many of which contain lipophilic and poorly water-soluble drugs in need of solubilizing excipients, such as cyclodextrins (CDs). However, CDs frequently reduce or even abolish the antimicrobial activities of commonly used pharmaceutical preservatives. The degree of inactivation depends on the CD complexation of the preservatives, which in turn depends on their chemical structure and physiochemical properties.

Chitosan and Anionic Solubility Enhancer Sulfobutylether-β-Cyclodextrin-Based Nanoparticles as Dexamethasone Ophthalmic Delivery System for Anti-Inflammatory Therapy.

Cataract surgery interventions are constantly increasing, particularly among adult and elderly patients. This type of surgery can lead to inflammatory states of the ocular anterior segment (AS), usually healed via postoperative treatment with dexamethasone (DEX)-containing eye drops. The application of eye drops is challenging due to the high number of daily administrations.

Anomalous Properties of Cyclodextrins and Their Complexes in Aqueous Solutions.

Cyclodextrins (CDs) are cyclic oligosaccharides that emerged as industrial excipients in the early 1970s and are currently found in at least 130 marketed pharmaceutical products, in addition to numerous other consumer products. Although CDs have been the subject of close to 100,000 publications since their discovery, and although their structure and properties appear to be trivial, CDs are constantly surprising investigators by their unique physicochemical properties. In aqueous solutions, CDs are solubilizing complexing agents of poorly soluble drugs while they can also act as organic cosolvents like ethanol.

Chitosan/sulfobutylether-β-cyclodextrin based nanoparticles coated with thiolated hyaluronic acid for indomethacin ophthalmic delivery.

Indomethacin (IND) is topically administered for the treatment of the anterior segment diseases such as conjunctivitis, uveitis, and inflammation prevention for post-cataract surgery, as well as posterior segment diseases as macular edema. Currently IND is available as 0.1% w/v hydroxypropyl-β-cyclodextrin-based eye drop formulation and its bioavailability is limited by several drawbacks such as the nasolacrimal duct draining, the reflex blinking and the low volume of the conjunctival sac.

Age-related ocular conditions: Current treatments and role of cyclodextrin-based nanotherapies.

Age-related eye disorders are chronic diseases that affect millions of people worldwide. They cause visual impairment and, in some cases, irreversible blindness. Drug targeting to the retina is still a challenge due to the difficulties with drug distribution, crossing eye barriers, and reaching intraocular tissues in an effective therapeutic concentration.

In Vitro and Ex Vivo Evaluation of Nepafenac-Based Cyclodextrin Microparticles for Treatment of Eye Inflammation.

The aim of this study was to design and evaluate novel cyclodextrin (CD)-based aggregate formulations to efficiently deliver nepafenac topically to the eye structure, to treat inflammation and increase nepafenac levels in the posterior segment, thus attenuating the response of inflammatory mediators. The physicochemical properties of nine aggregate formulations containing nepafenac/γ-CD/hydroxypropyl-β (HPβ)-CD complexes as well as their rheological properties, mucoadhesion, ocular irritancy, corneal and scleral permeability, and anti-inflammatory activity were investigated in detail. The results were compared with a commercially marketed nepafenac suspension, Nevanac 3 mg/mL.

Cyclodextrin⁻Amphiphilic Copolymer Supramolecular Assemblies for the Ocular Delivery of Natamycin.

Natamycin is the only drug approved for fungal keratitis treatment, but its low water solubility and low ocular penetration limit its efficacy. The purpose of this study was to overcome these limitations by encapsulating the drug in single or mixed micelles and poly(pseudo)rotaxanes. Soluplus and Pluronic P103 dispersions were prepared in 0.

Nepafenac-Loaded Cyclodextrin/Polymer Nanoaggregates: A New Approach to Eye Drop Formulation.

The topical administration route is commonly used for targeting therapeutics to the eye; however, improving the bioavailability of drugs applied directly to the eye remains a challenge. Different strategies have been studied to address this challenge. One of them is the use of aggregates that are formed easily by self-assembly of cyclodextrin (CD)/drug complexes in aqueous solution.

Cyclodextrin-based telmisartan ophthalmic suspension: Formulation development for water-insoluble drugs.

In this study, cyclodextrin-based aqueous eye drop suspension of the water insoluble drug telmisartan was developed. Formation of a drug/γ-cyclodextrin complex was enabled by preventing formation of a poorly water-soluble zwitterion using a volatile base that was removed upon drying of the complex powder. Hydroxypropyl methylcellulose was shown to have the overall best effect, stabilizing the complexes without hampering the drug release from the formulation.

Mucus as a barrier to lipophilic drugs.

Mucus is a complex hydrogel, comprising glycoproteins, lipids, salts, DNA, enzymes and cellular debris, covering many epithelial surfaces in the human body. Once secreted, mucin forms a barrier to protect the underlying tissues against the extracellular environment. Mucus can therefore adversely affect the absorption or action of drugs administered by the oral, pulmonary, vaginal, nasal or other routes.

Cyclodextrin solubilization of carbonic anhydrase inhibitor drugs: formulation of dorzolamide eye drop microparticle suspension.

Topically applied carbonic anhydrase inhibitors (CAIs) are commonly used to treat glaucoma. However, their short duration of action requiring multiple daily dosing can hamper patient compliance. The aim of this study was to develop novel aqueous CAI eye drop formulation containing self-assembled drug/cyclodextrin (D/CD) microparticles that enhance and prolong drug delivery to the eye.

Topical and systemic absorption in delivery of dexamethasone to the anterior and posterior segments of the eye.

Purpose: This study aimed to: (1) determine the relative efficiencies of topical and systemic absorption of drugs delivered by eyedrops to the anterior and posterior segments of the eye; (2) establish whether dexamethasone-cyclodextrin eyedrops deliver significant levels of drug to the retina and vitreous in the rabbit eye, and (3) compare systemic absorption following topical application to the eye versus intranasal or intravenous delivery.

Methods: In order to distinguish between topical and systemic absorption in the eye, we applied 0.5% dexamethasone-cyclodextrin eyedrops to one (study) eye of rabbits and not to the contralateral (control) eye.

Ocular powder: dry topical formulations of timolol are well tolerated in rabbits.

Purpose: Although eye drops are the most common form of ocular drugs, they have several limitations. Drug absorption into the eye is, in general, less than 5%, addition of preservatives is often necessary, and many drugs cannot be formulated as eye drops. Formulating ocular drugs as powder may solve these problems.

Assessment of mucoadhesion by a resonant mirror biosensor.

The aim of this study was to add knowledge to the existing theories of mucoadhesion and to review mucoadhesive polymers based on their ability to form non-covalent bonds with mucus glycoprotein. Resonant mirror biosensor was used to study the candidate mucoadhesive polymers hydroxypropyl methylcellulose, carboxymethylcellulose, Carbopol, hyaluronate, alginate and chitosan. Bovine submaxillary mucin was chosen as substrate, representing the major glycosylated protein in mucus.

Cyclodextrin formulation of dorzolamide and its distribution in the eye after topical administration.

Due to limited aqueous solubility of dorzolamide at physiologic pH, the pH of Trusopt eye drops (cont. 2% dorzolamide) has to be kept at about 5.65, and to increase the topical bioavailability of the drug from Trusopt the contact time of the drug with the eye surface is increased by increasing the viscosity of the eye drops to 100 cps.

Cyclodextrins and drug permeability through semi-permeable cellophane membranes.

Determinations of drug fluxes through semi-permeable cellophane membranes are used to evaluate cyclodextrin complexes and cyclodextrin containing drug formulations. In the present study we investigated how the cyclodextrin concentration, the membrane thickness and the molecular weight cut off (MWCO) of the membrane influence drug fluxes. The cyclodextrin used was 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) and the sample drug was hydrocortisone.