Article

Pulsatile drug delivery system using hydrogels

Department of Chemical Engineering, Waseda University, Tokyo, Japan
Advanced Drug Delivery Reviews (Impact Factor: 15.04). 07/1993; 11(1-2):85-108. DOI: 10.1016/0169-409X(93)90028-3

ABSTRACT

In recent years, temporal control of drug delivery has been of interest to achieve improved drug therapies. Intelligent drug delivery systems (DDS) are one expected result, demonstrating an ability to sense external environmental changes, judge the degree of external signal, and release appropriate amounts of drug. Intelligent DDS may be achieved using stimuli-responsive polymeric hydrogels which alter their structure and physical properties in response to external stimuli. Pulsatile drug release has the advantages of avoiding drug tolerance or matching the body's release of specific peptides or hormones. In this review, recent studies for pulsatile drug delivery in response to stimuli such as chemical agents, pH, electric fields, and temperature are discussed. Achievement of pulsatile drug release from stimuli-responsive polymeric hydrogels as on-off switches and its mechanism are reviewed in terms of control for stimuli-responsive swelling.

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    • "From the literature perspective, LCST is most commonly studied since all water-soluble polymers with intermediate hydrophilicity exhibit a LCST transition, including a wide range of homopolymers and almost unlimited number of different copolymers [15] [16] [17] [18] [19] [20] [21]. The LCST phase transition has also been exploited for a wide range of applications often in the biomedical field [17] [22], including drug delivery [15] [23], switchable surfaces for cell growth [24] [25] and actuators for microfluidic devices [26] [27], whereby the transition temperature can be easily tuned by copolymerization or by adding additives like salts or buffers [28– 31]. In contrast to the vast amount of literature on LCST polymers, much less studies are reported involving UCST polymers since a UCST phase transition is not commonly observed in aqueous polymer solutions. "
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    ABSTRACT: The development of responsive and multiresponsive polymers is gaining interest as they enable the development of more and more complex responsive materials. In this contribution, the synthesis and solubility behavior of well-defined poly(methyl acrylate) (PMA) and poly(diethylene glycol ethyl ether acrylate) (PDEGEA) homopolymers as well as PMA-block-PDEGEA block copolymers is reported. At first, a solubility screening of the homopolymers in ethanol-water solvent mixtures was performed in a high-throughput experimentation (HTE) manner using parallel turbidimetry, which revealed that in 35 wt% ethanol PMA undergoes an upper critical solution temperature (UCST) phase transition while PDEGEA undergoes a lower critical solution temperature phase transition in this solvent mixture. Moreover, the thermoresponsive self-assembly of PMA-b-PDEGEA block copolymers in water and ethanol were investigated by turbidimetry and DLS revealing UCST-induced disassembly of the micelles in ethanol and LCST-induced clustering of the micelles in water. Finally schizophrenic behavior of the PMA-b-PDEGEA block copolymers in 35 wt% ethanol is demonstrated.
    Full-text · Article · Apr 2015 · European Polymer Journal
    • "A drug should be delivered only when and/or where it is needed at the minimum required dose.[5] For the drugs to follow circadian rhythm, like in asthma, a reasonable and an acceptable rationale is a delivery system capable of releasing drugs in a pulsatile fashion rather than as a continuous delivery at the predetermined time/site following oral administration.[67] "
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    ABSTRACT: A tablet system consisting of cores coated with two layers of swelling and rupturable coatings was prepared and evaluated as time controlled chronomodulated tablet. Cores containing Montelukast sodium as model drug were prepared by direct compression and then coated sequentially with an inner swelling layer containing a HPMC E 5 and an outer rupturable layer of Eudragit RL/RS (1:1). A three-factor, two-level, full factorial design was used to investigate the influence of amount of HPMC E 5 and Eudragit RL/RS (1:1) on the responses, i.e., lag time to release and time required for 80% of drug to releases. The dissolution tests were studied using the USP paddle method at 50 rpm in 0.1 N HCL for 2 hr and than in phosphate buffer pH 6.8. Cores containing Montelukast sodium as model drug were prepared by direct compression and then coated sequentially with an inner swelling layer containing a HPMC E 5 and an outer rupturable layer of Eudragit RL/RS (1:1). A three-factor, two-level, full factorial design was used to investigate the influence of amount of HPMC E 5 and Eudragit RL/RS (1:1) on the responses, i.e., lag time to release and time required for 80% of drug to releases. The dissolution tests were studied using the USP paddle method at 50 rpm in 0.1 N HCL for 2 hr and than in phosphate buffer pH 6.8. The lag time of the drug release decreased by increasing the inner swelling layer and increased by increasing the rupturing layer level. The results obtain from present study suggest that swelling come reputable coating approach gives desire drug release after lag time.
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    • "zero order *Address correspondence to this author at the Laboratory of Organic Chemical Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-541 24 Thessaloniki, Greece; Tel: +30 2310 997812; Fax: +30 2310 997667; E-mail: dbic@chem.auth.gr release) [1] [2] [3] [4] [5] [6]. Ideally such systems aim to match drug release rate to a biological requirement of a given disease therapy and thus to manage the disease while minimizing treatment's side effects. "
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    ABSTRACT: Pulsatile drug delivery aims to release drugs on a programmed pattern i.e.: at appropriate time and/or at appropriate site of action. Currently, it is gaining increasing attention as it offers a more sophisticated approach to the traditional sustained drug delivery i.e: a constant amount of drug released per unit time or constant blood levels. Technically, pulsatile drug delivery systems administered via the oral route could be divided into two distinct types, the time controlled delivery systems and the site-specific delivery systems. The simplest pulsatile formulation is a two layer press coated tablet consisted of polymers with different dissolution rates. Homogenicity of the coated barrier is mandatory in order to assure the predictability of the lag time. The disadvantage of such formulation is that the rupture time cannot be always adequately manipulated as it is strongly correlated with the physicochemical properties of the polymer. Gastric retentive systems, systems where the drug is released following a programmed lag phase, chronopharmaceutical drug delivery systems matching human circadian rhythms, multiunit or multilayer systems with various combinations of immediate and sustained-release preparation, are all classified under pulsatile drug delivery systems. On the other hand, site-controlled release is usually controlled by factors such as the pH of the target site, the enzymes present in the intestinal tract and the transit time/pressure of various parts of the intestine. In this review, recent patents on pulsatile drug delivery of oral dosage forms are summarized and discussed.
    Full-text · Article · Feb 2009
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