Recent Patents on Drug Delivery & Formulation - Volume 4, Issue 2, 2010

In Vitro-In Vivo Correlation (IVIVC) is being increasingly used to predict bioperformance of dosage forms without conducting animal and/or human studies which are not only time-consuming and expensive but also might be considered ethically undesirable. The main aim of IVIVC methods is to develop in vitro drug release methods which are simple, robust, reproducible, inexpensive, in compliance with compendial and regulatory requirements and finally can be used in lieu of in vivo studies to direct formulation selection. This review provides a summary of currently marketed polymeric depot products and the patents related to these drug delivery systems in addition to currently available in vitro release methods used to study drug release from injectable controlled release drug delivery systems, currently available IVIVC methods and some examples of successful IVIVC for small molecules, peptides and proteins formulated in controlled release formulations administered subcutaneously or intramuscularly.

The field of regenerative medicine offers nowadays the potential to significantly impact a wide spectrum of healthcare issues, from insulin-dependent diabetes mellitus (Type 1 diabetes, T1D) to cardiovascular disease. In tissue engineering biomaterials, biological factors, regeneration competent cells are used in the process of creating functional tissue. Regarding the type of stem or progenitor cells which represents the best candidate for therapy, embryonic stem cells have been considered the master cells capable of differentiating into every type of cells either in vitro or in vivo, in spite of serious ethical concerns. Nevertheless, experimental evidence suggests that adult stem cells and even terminally differentiated somatic cells under appropriate micro environmental treatments can be reprogrammed and contribute to a much wider spectrum of differentiated progeny than previously anticipated. One of the main goals is to exploit novel technologies aiming to isolate, expand and enrich sources of regeneration competent cells, especially adult somatic stem cells. Researchers are also trying to develop innovative strategies for effectively delivering regenerative cell populations and to implement ‘tracking’ tools to verify their engraftment and destiny in vivo. Here we review recent patents on the field issued over the past five years.

Majority of infectious microorganism make their gateway to the host through mucosal surfaces, such as gastrointestinal tract, nasal and vaginal tract. Mucosal immune response structured as sIgA can effectively prevent the attachment and invasion of the microorganism from mucosal surface and thereby serves as an efficient tool against infectious disease. There has been an increased demand for the development of novel vaccine that leads to the induction of immune response in systemic circulation as well as at mucosal surfaces against infectious disease. Mucosal delivery of vaccine provides basis for induction of both mucosal as well as systemic immune responses against the infectious organisms. However, a variety of factors such as mucociliary clearance, presence of deteriorating enzymes, pH extremes (GIT), low permeation and metabolic degradation limit the mucosal delivery of vaccine. Numerous strategies have been explored in the meadow of mucosal vaccination for the purpose of efficient antigen delivery through mucosal route(s). Polymeric carrier(s) such as nanoparticles and microparticles loaded with the antigen can serve as the basis for creation of important formulations for improved vaccine. Biodegradable and mucoadhesive polymeric carrier(s) seems to be most promising candidate for mucosal vaccine delivery. Several polymers from natural and synthetic origin, such as polylactide- co-glycolide, chitosan, alginate, carbopol, gelatin etc., have been explored for the efficient mucosal vaccine delivery and significant results have been obtained. This review outlines the polymers used in mucosal vaccine delivery with special reference to mucoadhesive/biodegradable polymers. This article also covers the recent patent granted in the field on polymeric carrier mediated mucosal vaccination.

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.

The present article dwells in reviewing critically the patents published mainly on the new emerging trends and techniques for increasing the bioavailability of silymarin, the polyphenolic fraction obtained from the seeds of Silybum marianum. The use of this herb for treating various ailments like hepatitis, cirrhosis, jaundice, mushroom and toxin poisoning is well known. But the potential use of this herbal drug is limited due to the poor absorption and poor bioavailability after oral administration. The belief that the natural medicines are much safer than synthetic drugs, has gained popularity in recent years and led to tremendous growth of phytopharmaceutical usage and thus the need of improving the bioavailability by various means like complexation, derivatization, solubilization, targeted delivery, controlled delivery and many other miscellaneous techniques.

Upon implantation or insertion into patient's body for exerting the intended purpose like salvage of normal functions of vital organs, the medical devices are unfortunately becoming the sites of competition between host cell integration and microbial adhesion. Moreover, since there is an increased use of implanted medical devices, the incidence of biofilm-and medical devices-related nosocomial infections is also increasing progressively. To control microbial colonization and subsequent biofilm formation of the medical devices, different approaches either to enhance the efficiency of certain antimicrobial agents or to disrupt the basic physiology of the pathogenic microorganisms including novel small molecules and antipathogenic drugs are being explored. In addition, the various lipid-and polymer-based drug delivery carriers are also investigated for applying antibiofilm coating of the medical devices especially over catheters. The main intention of this review is therefore to summarize the major and/breakthrough inventions disclosed in patent literatures as well as in research papers related to microbial colonization of medical devices and novel preventive strategies. This review starts with an overview of the preventive strategies followed by a short description about the potential of different lipidic-and polymeric-drug delivery carriers in eradicating the biofilm-associated infections from the medical devices.

The patents annotated in this section have been selected from various patent databases. These recent patents are relevant to the articles published in this journal issue, categorized by therapeutic areas/targets and therapeutic agents related to drug delivery and formulations.