Release of insulin from pH-sensitive poly(ortho esters)

Controlled-release dosage forms enhance the safety, efficacy, and reliability of drug therapy. They regulate the drug release rate to control drug action and reduce the frequency of drug administration to encourage patients to comply with dosing instructions. Conventional dosage forms often lead to wide swings in serumdrug concentrations. Most of the drug content is released soon after administration, causing drug levels in the body to rise rapidly, peak, and then decline sharply. For drugs whose actions correlate with their serumdrug concentration, these sharp fluctuations often cause unacceptable side effects at the peaks, followed by inadequate therapy at the troughs (Fig. 1). Administering smaller doses at more frequent intervals can damp concentration fluctuations, preventing over-and underdosing, but the inconvenience may cause patients to skip or delay doses, degrading efficacy. Compliance, measured as the percentage of patients taking 95% to 105% of prescribed oral medications, decreased from 67% with once-a-day regimens to 22% with four-times-a-day regimens (1). These difficulties are especially pronounced with drugs that have short half-lives and a narrow range of safe and effective concentrations. Precisely controlled release is particularly valuable for such agents (see Drug delivery systems).The term controlled release technology generally refers to a variety of methods used to exert various degrees of control over drug release. The U.S. Food and Drug Administration (FDA) defines controlled release dosage forms as those formulations designed to release active ingredient(s) at rates that differ significantly from their corresponding immediate release forms (2). The indexing system of Index Medicus supports this broad definition by classifying these dosage forms as delayed-action preparations, and Excerpta Medica uses the index term sustained release preparations. The pharmaceutical literature contains a profusion of terms, including delayed-action, extended action, gradual release, prolonged release, protracted release, slow release, sustained release, depot, retard, and timed-release dosage forms, all emphasizing an increased duration of action (3).To avoid confusion, several researchers have incorporated therapeutic intention into the definition of controlled release (4-7). Thus, controlled-release pharmaceuticals release drugs in vivo according to a predictable, therapeutically rational, programmed rate to achieve the optimal drug concentration in the minimal time (4). Specification by release rate complements specification by quantity; jointly considered, they fix the duration of drug release. Therefore, the drug's duration of action can become a design property of a controlled release dosage form rather than an inherent pharmacokinetic property of the drug molecule.Under this more precise definition, controlled release drug delivery not only provides a predictable, patterned action, but controls the rate of drug release for a predetermined period. Controlled release systems deliver drugs at a con...

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“…Systems with physical mechanisms are discussed here; a description of chemical mechanisms, such as pH-sensitive hydrogels, is available (107).…”

Section: Ph Sensitivitymentioning

confidence: 99%

Controlled Release Technology, Pharmaceutical

Edgren

Leeper

Nichols

et al. 2000

Kirk-Othmer Encyclopedia of Chemical Technology

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“…Bioerodible insulin delivery devices, based on the same principle of pH lowering, are also being investigated [15].…”

Section: Self-regulating Delivery Systems For Insulinmentioning

confidence: 99%

Delivery of hormones: some new concepts

Hermens

1992

Pharmaceutisch Weekblad Scientific Edition

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Some new concepts in the delivery of hormones are described. Transmucosal or transdermal penetration of hormones can be facilitated, often by the use of absorption enhancers. Studies of nasal insulin delivery are described. Recently developed iontophoretic delivery devices can be useful for pulsatile transdermal administration of peptide hormones. A self-regulating delivery system releasing insulin in response to glucose levels is described. A vaginal ring releasing ethinylestradiol and 3-ketodesogestrel is a new concept in long-acting contraception. A nasal estradiol formulation, containing the absorption enhancer dimethyl-beta-cyclodextrin, is an interesting alternative to oral and transdermal delivery of female sex hormones.

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“…The pH-sensitive hydrogels containing pendant acidic or basic groups such as carboxylic acids, sulphonic acids, primary amines, or ammonium salts which change ionization in response to change in the pH have become the subject matter of major interest for use as carriers in oral drug delivery research (15,16). The extent of interaction, adhesion, and uptake of nanoparticles of broad spectrum sizes after oral administration have been reported to be highest for the smallest particles (11).…”

Section: Introductionmentioning

confidence: 99%