A two pulse drug delivery system for amoxicillin: an attempt to counter the scourge of bacterial resistance against antibiotics.

Bearing in mind the present scenario of the increasing biological tolerance of bacteria against antibiotics, a time controlled two pulse dosage form of amoxicillin was developed. The compression coating inlay tablet approach was used to deliver the drug in two pulses to different parts of the GIT after a well defined lag time between the two releases. This was made possible by formulating a core containing one of the two drug fractions (intended to be delivered as the second pulse), which was spray coated with a suspension of ethyl cellulose and a hydrophilic but water insoluble agent as a pore former (microcrystalline cellulose). Coating of up to 5% (m/m) was applied over the core tablet, giving a corresponding lag of 3, 5, 7 and 12 h. Increasing the level of coating led to retardation of the water uptake capacity of the core, leading to prolongation of the lag time. Microcrystalline cellulose was used as a hydrophilic but water insoluble porosity modifier in the barrier layer, varying the concentration of which had a significant effect on shortening or prolongation of the lag time. This coated system was further partially compression coated with the remaining drug fraction (to be released as the first immediate release pulse) with a disintegrant, giving a final tablet. The core tablet and the final two pulse inlay tablet were further investigated for their in vitro performance.

Chronopharmaceutics: a promising drug delivery finding of the last two decades.

Pulsatile drug delivery system capable of releasing the drug after a predetermined lag period in pulsed or controlled release manner recently has drawn the attention of both academic and industrial research. Depending on the effective therapeutic application of the drug, a variety of design strategies have been formulated in the pursuit of pulsatile release. Circadian (24 hr cycle) dependency of various physiological and pathological functions is well established, thus, it becomes imperative to develop a drug delivery system to achieve release of drug at specific site and time. Such systems are advantageous for drugs which have an extensive first pass metabolism, biological tolerance, needs targeting of locally absorbed / active drug to a specific site in intestine and are useful for the therapy for chronopharmacological needs. This manuscript portrays the important patents related to chronomodulated release system such as system with eroding, rupturing or soluble barrier coatings. In addition, recently developed chronotherapeutic dosage forms including tablets, capsules, pellets, beads implants, osmotic pump, liposome, thermoresponsive, inflammation stimuli sensitive, electrical stimuli sensitive, ultrasound stimuli responsive, magnetic stimuli responsive etc., are also conferred.

Distinctive features of "chronotherapeutic" and "pulsatile" drug delivery systems negating the practice of their interchangeable terminology.

The term pulsatile drug delivery has often been used as a synonym to chronotherapeutic drug delivery. This needs to be given a thought as both the drug delivery systems are entirely addressing different needs of the patients as well as the intentions of the formulators being different. Chronotherapeutic systems are based completely on circadian needs and response of the body and the need of the drug to be in its maximum concentrations at a particular time of the day, the fact being supported by endless list of ailments which elicit the related symptoms at a particular time of the day. Considering the formulation approach, one does not find major differences among site-specific chronotherapeutic systems and the basic and more conventional intestinal or colon targeted systems due to the mechanism and the site of landing of drug of both being almost similar even though the intention of the formulator being different. An ideal pulsatile system is the one delivering drug in different pulses with multiple troughs in release profile. The article explores the major differences in between the two systems and highlights the need of using appropriate terminology for these individual and distinct systems catering different needs.

Recent advances in pelletization technique for oral drug delivery: a review.

Multiparticulate dosage forms are receiving a great deal of attention as alternative system for oral drug delivery. The present review outlines the recent findings on the manufacturing and evaluation of spherical pellets published over the past decade. The techniques namely extrusion-spheronization, hot melt extrusion, freeze pelletization, cryopelletization have been discussed along with parameters affecting pelletization. Evaluation of quality of the pellets is discussed with reference to the size distribution, shape, surface morphology, specific surface area, friability, tensile strength, density, porosity, disintegration time and in vitro dissolution studies of pellets. The use of multiparticulate dosage forms as a promising system for the oral delivery of many therapeutic agents has also been examined in the current review.

Multiple-pulse drug delivery systems: setting a new paradigm for infectious disease therapy.

BACKGROUND: Pulsatile drug delivery of actives based on the body's biological rhythms came into sight as a novel and emerging concept in the field of drug delivery. The concept of late has given birth to another field of research worth exploring: multiple-pulse drug delivery. OBJECTIVE: Delivering a drug in multiple pulses has been applied to antibiotics for effective and patient compliant drug delivery. Delivering antibiotics in divided pulses results in better annihilation of microbes, as it prevents them going into a resistant/dormant stage and developing biological tolerance. The concept appears to have potential, and on 16 March 2009 MiddleBrook Pharmaceuticals, Inc. will launch the first of such once-daily product based on their proprietary pulsatile drug delivery technology, PULSYS. METHODS: This review focuses on the rationale, possible strategies and technologies employed for multiple-pulse delivery, as well as current status and future trends. CONCLUSION: The concept is in its infancy and promises great potential in the fight against microbial resistance; many approved formulations based on similar approaches with new and improved therapeutic paradigms are anticipated in the near future.

Site specific chronotherapeutic drug delivery systems: a patent review.

Oral dosage forms are known to provide a zero order or first order release in which the drug is released at a substantially steady rate of release per unit of time. However, there are instances where maintaining a constant blood level of a drug is not desirable. In such cases a pulsatile drug delivery may be more advantageous. Pulsatile drug delivery systems can be classified into site-specific systems in which the drug is released at the desired site within the intestinal tract (e.g., the colon), or time-controlled devices in which the drug is released after a well-defined time period. Environmental factors like pH or enzymes present in the intestinal tract control the release of a site-controlled system whereas the drug release from time-controlled systems is controlled primarily by the delivery system and not by the environment. The delayed liberation of orally administered drugs has been achieved through a range of formulation approaches, including single or multiple unit systems provided with release-controlling coatings, capsular devices and osmotic pumps. Our aim in this review is to outline the rational and prominent design strategies behind site-specific oral pulsatile delivery. The present article provides a good patent review regarding the Site Specific Chronotherapeutic Drug Delivery Systems.