Mucoadhesive ocular insert based on thiolated poly(acrylic acid): development and in vivo evaluation in humans

• Published in: Journal of controlled release Vol. 89; no. 3; pp. 419 - 428
• Main Authors: Hornof, Margit, Weyenberg, Wim, Ludwig, Annick, Bernkop-Schnürch, Andreas
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 20.05.2003; Elsevier
• Subjects: Acrylic Resins - administration & dosage; Acrylic Resins - pharmacokinetics; Adhesives - administration & dosage; Adult; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cornea - drug effects; Cornea - metabolism; Diclofenac; Drug Delivery Systems - methods; Female; Fluorescein - administration & dosage; Fluorescein - pharmacokinetics; Fluorophotometry; General pharmacology; Humans; In vivo; Male; Medical sciences; Middle Aged; Ocular drug delivery; Ocular insert; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poly(acrylic acid)–Cysteine conjugate; Thiomers; In vivo; Ocular insert; Thiomers; Poly(acrylic acid)–Cysteine conjugate; Ocular drug delivery; Fluorophotometry; Diclofenac; Thiol polymer; Cysteine; Toxicity; Poly(acrylic acid)-Cysteine conjugate; Drug carrier; Insert; Eye; Bioadhesive system; Release; Human; Pharmaceutical technology; Controlled release form; Control release polymer; Normal; In vitro; Non steroidal antiinflammatory agent; Arylacetic acid derivatives; Acrylic acid polymer; Dosage form; Active ingredient; Conjugated compound; Pharmacokinetics
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(03)00135-4

The aim of the study was to develop a mucoadhesive ocular insert for the controlled delivery of ophthalmic drugs and to evaluate its efficacy in vivo. The inserts tested were based either on unmodified or thiolated poly(acrylic acid). Water uptake and swelling behavior of the inserts as well as the drug release rates of the model drugs fluorescein and two diclofenac salts with different solubility properties were evaluated in vitro. Fluorescein was used as fluorescent tracer to study the drug release from the insert in humans. The mean fluorescein concentration in the cornea/tearfilm compartment as a function of time was determined after application of aqueous eye drops and inserts composed of unmodified and of thiolated poly(acrylic acid). The acceptability of the inserts by the volunteers was also evaluated. Inserts based on thiolated poly(acrylic acid) were not soluble and had good cohesive properties. A controlled release was achieved for the incorporated model drugs. The in vivo study showed that inserts based on thiolated poly(acrylic acid) provide a fluorescein concentration on the eye surface for more than 8 h, whereas the fluorescein concentration rapidly decreased after application of aqueous eye drops or inserts based on unmodified poly(acrylic acid). Moreover, these inserts were well accepted by the volunteers. The present study indicates that ocular inserts based on thiolated poly(acrylic acid) are promising new solid devices for ocular drug delivery.