methylcellulose and cetyl-alcohol

For patients with conditions requiring chronic rather than acute therapy, the advantages of collagen shields in providing high and sustained levels of drugs and/or lubricants to the cornea are outweighed by the difficulty of insertion of the shield and the problem of blurred vision. We have developed a delivery system in which collagen pieces suspended in a viscous vehicle can be instilled into the lower forniceal space, thereby simplifying application and reducing blurring of vision. The collagen pieces (Collasomes) can be formulated with various constituents such as antibiotics or cyclosporine, or with chemical alterations such as the inclusion of a lipid (Lacrisomes) for the treatment of dry eyes. In the normal eyes of volunteers, Collasomes hydrated in a solution of sodium fluorescein and suspended in a methylcellulose vehicle as a model for delivery of water-soluble drugs produced fluorescein concentrations 17 to 42 times higher in the cornea and 6 to 8 times higher in the aqueous humor, compared with fluorescein-containing vehicle alone. In a preliminary controlled study, 76% of patients with moderately severe keratoconjunctivitis sicca (KCS) preferred Lacrisomes to the vehicle control because of a more soothing effect and longer duration of comfort. All preparations were well tolerated by all study subjects. Current studies involve improving drug delivery by chemically modifying the collagen molecule to slow diffusion of the drug from the Collasome matrix, as well as varying the amount of cetyl alcohol and combining it with modified collagen in Lacrisomes to maximize comfort in patients with dry eyes.

Topics: Adult; Aged; Aged, 80 and over; Collagen; Double-Blind Method; Drug Delivery Systems; Fatty Alcohols; Female; Humans; Keratoconjunctivitis Sicca; Male; Methylcellulose; Middle Aged; Ophthalmic Solutions

Salting-out effects were utilized for developing a multiparticulate system balancing numbness masking and high bioavailability. A "salting-out taste-masking system" consisting of a drug core containing acetaminophen as a model drug, a salting-out layer containing sodium carbonate (Na(2)CO(3)) and hydroxypropylmethylcellulose (HPMC), and a water-penetration-control layer consisting of cetanol was designed and prepared. The system successfully generated a long lag time while achieving immediate drug release. In the system, the Na(2)CO(3) release rate was slower and the lag time was longer than when the water-penetration-control layer was not present. During the release of Na(2)CO(3) from the system, the release of HPMC and drug was suppressed. These results indicated that the water-penetration-control layer maintained a high concentration of Na(2)CO(3), prevented HPMC's dissolution, and generated a long lag time of drug release. The system generated longer lag time and released drug more immediately than formulation containing the water-penetration-control layer of same thickness without the salting-out layers. These results indicated the salting-out layers were necessary for obtain a long lag time and subsequent immediate drug release. This novel taste-masking system has the potential to be a useful multiparticulate dosage form for effective, safe, and user-friendly drug therapy.

Topics: Acetaminophen; Biological Availability; Carbonates; Chemistry, Pharmaceutical; Fatty Alcohols; Hypromellose Derivatives; Methylcellulose; Pharmaceutical Preparations; Salts; Solubility; Taste; Time Factors

A novel oral controlled delivery system for propranolol hydrochloride (PPL) was developed and optimized using wet granulation process. We are studying the ability of subcoating with Kollidon VA 64 as a barrier to water penetration in matrix cores combined hydrophilic (native dextran-HPMC)/hydrophobic (cetyl alcohol) prior to film coating with Opradry II-YS-30-18056. The copovidone (i.e., Kollidon VA 64) not only increases the mechanical properties of tablets (less friability) but also reduces the amount of absorbed water from the air in tropical stability condition (25 degrees C and 75% relative humidity). The in vitro dissolution profiles of coated sustained-release matrix tablets of racemic PPL were determined and compared with uncoated tablet cores according to the United States Pharmacopeia (USP) Tolerance Specifications for Propranolol Hydrochloride Extended-Release Capsules. A comparative kinetic study of the present matrix tablets (coated and uncoated cores) and commercial SUMIAL RETARD capsules (reference formulation (R) (Spain) was established). The values for the similarity factor (f2=61.756, f2=72.326 and f2=88.509 for initial time, one year and two years, respectively (uncoated cores vs. capsule) and f2=63.904, f2=69.502 and f2=76.348 (coated tablets vs. capsule) for initial time, one year and 2 two years, respectively) suggested that the dissolution profiles of the present three sustained-release oral dosage forms are similar and stable during two years under stability condition.

Topics: Chemistry, Pharmaceutical; Delayed-Action Preparations; Dextrans; Drug Compounding; Excipients; Fatty Alcohols; Hypromellose Derivatives; Kinetics; Methylcellulose; Models, Statistical; Povidone; Tablets; Tablets, Enteric-Coated; Technology, Pharmaceutical; Temperature; Time Factors

A novel oral controlled delivery system for propranolol hydrochloride (PPL) was developed and optimized. The in vitro dissolution profiles of sustained-release matrix tablets of racemic PPL were determined and compared with the United States Pharmacopeia (USP) tolerance specifications for Propranolol Hydrochloride Extended-Release Capsules. The influence of matrix forming agents (native dextran, hydroxypropyl methylcellulose (HPMC), cetyl alcohol) and binary mixtures of them on PPL release in vitro was investigated. A central composite design was applied to the optimization of a sustained-release tablet formulation. The sustained-release matrix tablets with good physical, mechanical and technological properties were obtained with a matrix excipient:PPL ratio of 60:40 (w/w), with a dextran:HPMC ratio of 4:1 (w/w) and with a cetyl alcohol amount of 15% (w/w). A comparative kinetic study of the present matrix tablets and commercial SUMIAL RETARD capsules (Spain) was established. The value for the similarity factor (f(2)=69.6) suggested that the dissolution profile of the present two sustained-release oral dosage forms are similar. Higuchi (diffusion) and Hixon-Crowell (erosion) kinetic profiles were achieved and this codependent mechanism of drug release was established.

Topics: Capsules; Carboxymethylcellulose Sodium; Chemistry, Pharmaceutical; Delayed-Action Preparations; Dextrans; Fatty Alcohols; Hardness; Hypromellose Derivatives; Methylcellulose; Propranolol; Solubility; Tablets

The release mechanism of high molecular weight fluorescein isothiocyanate dextrans (FITC-dextrans) from HPMC hydrogel matrices was studied. An anomaly was noted in the release behaviour of a series of high molecular weight FITC-dextrans from a tablet formulation designed to float in stomach contents. The tablets contained sodium bicarbonate and hydroxypropylmethyl cellulose (HPMC) in a cetyl alcohol matrix. When hydrated in an acid medium, this tablet consisted of a mixed solid with a viscous surface layer containing carbon dioxide bubbles through which the active ingredient (FITC-dextran) was released into the aqueous environment. However, it was observed that, above a critical molecular weight (approx. 65 kDa), the FITC-dextran was only released into the medium by an erosion-type mechanism, whereas, below this value, both diffusion and erosion processes took place. The key constraint appeared to be the apparent gel pore-size of the hydrated HPMC that was approximately 12 nm in diameter, irrespective of the molecular weight of the HPMC samples evaluated. It was concluded that FITC-dextran release was controlled by both FITC-dextran molecular weight and the HPMC hydrogel structure.

Topics: Dextrans; Fatty Alcohols; Fluorescein-5-isothiocyanate; Hydrogel, Polyethylene Glycol Dimethacrylate; Lactose; Methylcellulose; Molecular Weight; Oxazines; Tablets