Design and Gamma-Scintigraphic Evaluation of a Floating and Pulsatile Drug Delivery System Based on an Impermeable Cylinder

Abstract

Using current release technology, it is possible for many drugs oral delivery for a pulsed or pulsatile release, which is defined as the rapid and transient release of a certain amount of molecules within a short time-period immediately after a predetermined off-release period.1) Such novel drug delivery has been attempted for: (i) chronopharmacotherapy of diseases which show circadian rhythms in their pathophysiology 2) ; (ii) avoiding degradation of active ingredients in upper GI tract, e.g. proteins and peptides 3) ; (iii) for time programmed administration of hormones and many drugs such as isosorbide dinitrate, respectively to avoid suppression of normal secretion of hormones in body that can be hampered by constant release of hormone from administered dosage form and development of resistance [4][5][6][7][8][9] ; (iv) avoiding pharmacokinetic drug-drug interactions between concomitantly administered drugs. 10)Verapamil hydrochloride (Ver) was chosen as model drug, for it is a potent calcium-channel blocker and has been effective for preventing the time-related occurrence of ischemic. 11)Verapamil HCl has a distinct pH-dependent solubility in the pH-range of the gastrointestinal tract.12) The following solubility values have been reported: Ͼ150, 2.71 and 0.75 mg/ml at pH 1.2, 6.8 and 7.4, respectively.13) With conventional pulsatile release dosage forms, a possible decrease in the release rate when passing from the stomach into the intestine can result in in vivo variability and bioavailability problems. Thus can result in incomplete drug absorption from the pulsatile release system with the lag time more than the relatively brief gastric emptying time 14) and may lead to diminished efficacy of the administered dose. Overall, these considerations have led to the development of oral pulsatile release dosage forms possessing gastric retention capabilities.Floating-pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. Over the last three decades, various approaches have been pursued to increase the retention of an oral dosage form in the stomach, including floating systems, swelling and expanding systems, bioadhesive systems, modified-shape systems, high-density systems, and other delayed gastric emptying devices.14-16) The dosage forms with hydrodynamically balanced systems possessing gastric retention capabilities have a bulk density lower than gastric fluids and thus remain buoyant in the stomach without affecting the gastric emptying rate for a prolonged period of time.The present study focused on development and evaluate of a multifunctional drug delivery system, which was designed as a floating-pulsatile drug delivery system. Such drug delivery system is developed from the pulsatile system described by Krögel and Bodmeier 17,18) (Fig. 1, case 1). The novel system consists of a drug tablet placed within an impermeable polymeric cylinder closed with an erodible drug-free plug and floating material filled at the bottom (Fig. 1, case...

Gastroretentive dosage forms: A review with special emphasis on floating drug delivery systems

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A Novel In Situ Gel Formulation of Ranitidine for Oral Sustained Delivery

“…Several methods, both in vitro and in vivo , have been used to evaluate transport rates (Zou et al ., 2007). Advantages of the gamma scintigraphic technique lie in the ability to non-invasively monitor the deposition and clearance of drug formulations, allowing both quantitative and photographic illustrations of distribution and clearance of the radio labeled formulation.…”

Time and/or site specific drug delivery of floating pulsatile release delivery system

“…[33] System was to develop and evaluate a floating and pulsatile drug delivery system based on an impermeable cylinder. Pulsatile capsule was prepared by sealing the drug tablet and the buoyant material filler inside the impermeable capsule body with erodible plug.…”