Showing papers in "Recent Patents on Drug Delivery & Formulation in 2008"

Microemulsions: a novel approach to enhanced drug delivery.

Abstract: Microemulsions are isotropic, thermodynamically stable transparent (or translucent) systems of oil, water and surfactant, frequently in combination with a cosurfactant with a droplet size usually in the range of 20-200 nm. They can be classified as oil-in-water (o/w), water-in-oil (w/o) or bicontinuous systems depending on their structure and are characterized by ultra low interfacial tension between oil and water phases. These versatile systems are currently of great technological and scientific interest to the researchers because of their potential to incorporate a wide range of drug molecules (hydrophilic and hydrophobic) due to the presence of both lipophilic and hydrophilic domains. These adaptable delivery systems provide protection against oxidation, enzymatic hydrolysis and improve the solubilization of lipophilic drugs and hence enhance their bioavailability. In addition to oral and intravenous delivery, they are amenable for sustained and targeted delivery through ophthalmic, dental, pulmonary, vaginal and topical routes. Microemulsions are experiencing a very active development as reflected by the numerous publications and patents being granted on these systems. They have been used to improve the oral bioavailability of various poorly soluble drugs including cyclosporine and paclitaxel as professed by Hauer et al., US patent 7235248, and Gao et al., US patent 7115565, respectively. Furthermore, they can be employed for challenging tasks such as carrying chemotherapeutic agents to neoplastic cells and oral delivery of insulin as diligently described by Maranhao, US patent 5578583 and Burnside et al., US patent 5824638 respectively. The recent commercial success of Sandimmune Neoral (Cyclosporine A), Fortovase (Saquinavir), Norvir (Ritonavir), etc. also reflects the tremendous potential of these newer drug therapeutic systems. A critical evaluation of recent patents claiming different approaches to improve the drug delivery is the focus of the current review.

Orally disintegrating systems: innovations in formulation and technology.

Abstract: Orally disintegrating systems have carved a niche amongst the oral drug delivery systems due to the highest component of compliance they enjoy in patients especially the geriatrics and pediatrics. In addition, patients suffering from dysphagia, motion sickness, repeated emesis and mental disorders prefer these medications because they cannot swallow large quantity of water. Further, drugs exhibiting satisfactory absorption from the oral mucosa or intended for immediate pharmacological action can be advantageously formulated in these dosage forms. However, the requirements of formulating these dosage forms with mechanical strength sufficient to with stand the rigors of handling and capable of disintegrating within a few seconds on contact with saliva are inextricable. Therefore, research in developing orally disintegrating systems has been aimed at investigating different excipients as well as techniques to meet these challenges. A variety of dosage forms like tablets, films, wafers, chewing gums, microparticles, nanoparticles etc. have been developed for enhancing the performance attributes in the orally disintegrating systems. Advancements in the technology arena for manufacturing these systems include the use of freeze drying, cotton candy, melt extrusion, sublimation, direct compression besides the classical wet granulation processes. Taste masking of active ingredients becomes essential in these systems because the drug is entirely released in the mouth. Fluid bed coating, agglomeration, pelletization and infusion methods have proven useful for this purpose. It is important to note that although, freeze dried and effervescent disintegrating systems rapidly disintegrate in contact with fluids, they do not generally exhibit the required mechanical strength. Similarly, the candy process cannot be used for thermolabile drugs. In the light of the paradoxical nature of the attributes desired in orally disintegrating systems (high mechanical strength and rapid disintegration), it becomes essential to study the innovations in this field and understand the intricacies of the different processes used for manufacturing these systems. This article attempts at discussing the patents relating to orally disintegrating systems with respect to the use of different formulation ingredients and technologies.

Recent advances and patents on solid lipid nanoparticles.

Abstract: Solid Lipid Nanoparticles (SLNs) have attracted increasing scientific and commercial attention as colloidal drug carriers during the last decade. They have emerged as a potential alternative compared to other colloidal systems like polymeric nanoparticles, liposomes and fat emulsions, as they have been claimed to combine their advantages but successfully overcome their drawbacks. SLN formulations are extensively developed and characterized for their in vitro and in vivo applications by various routes like parenteral, oral, pulmonary, ocular, and dermal. SLNs are being widely investigated as carriers for delivery of macromolecules like proteins, oligonucleotides and DNA. SLNs have already been taken up for medium and large scale production using two of its reported production methods. In fact, the first SLN based product has recently been introduced in the Poland market as a topically applied moisturizer. Newer methods for production of SLNs and their applications are being reported and patented. Nanostructured lipid carriers (NLC) are mixture of solid lipid and liquid lipid while Lipid Drug Conjugates (LDC) are water insoluble lipid carrier for loading of poorly lipid soluble drugs. These new generation of lipid nanoparticles have been claimed to overcome the shortcomings of SLNs. This article reviews the formulation, characterization, applications, and patents on the advances and research on SLNs, NLC and LDC.

Recent Patents Review on Intranasal Administration for CNS Drug Delivery

Abstract: The treatment of brain disorders is the greatest challenge because of a variety of formidable obstacles in effective drug delivery and maintaining therapeutic concentrations in the brain for a prolonged period. The brain is a delicate organ, and evolution built very efficient ways to protect it. The same mechanisms that protect it against intrusive chemicals can also frustrate therapeutic interventions. Approximately, 100% of large molecule drugs and >98% of small molecule drugs do not cross the blood-brain barrier (BBB). Many advanced and effective approaches to brain delivery of drugs have emerged in recent years. Intranasal drug delivery is one of the important delivery options for brain targeting, as the brain and nose compartments are connected to each other via the olfactory/trigeminal route and via peripheral circulation. Realization of nose to brain transport and the therapeutic viability of this route can be traced from the ancient times and has been investigated for rapid and effective transport in the last two decades. Many patents have been filed in recent past, claiming enhanced delivery of intranasally administered therapeutics to the brain via olfactory/trigeminal neural pathways, use of novel devices for targeted delivery to olfactory region etc. Various models have been designed and studied by scientists to establish the qualitative and quantitative transport through nasal mucosa to brain. The development of nasal drug products for brain targeting is still faced with enormous challenges. A better understanding in terms of properties of the drug candidate, nose to brain transport mechanism, and transport to and within the brain is of utmost importance. A critical review of recent patents claiming different approaches for enhanced brain delivery through the nasal route will help in determining the focus of this promising area of research.

Mucoadhesive polymers for delivery of drugs to the oral cavity.

Abstract: Local therapy of the oral cavity is used to treat conditions such as gingivitis, oral candidosis, oral lesions, dental caries, xerostoma and oral carcinomas. Delivery systems used include mouthwashes, aerosol sprays, chewing gums, bioadhesive tablets, films, gels and pastes. There are three major problems associated with drug therapy within the oral cavity: rapid elimination of drugs due to the flushing action of saliva or the ingestion of food, the non-uniform distribution of drugs within saliva on release from a solid or semisolid delivery system and patient compliance in terms of taste. Prolonged contact time of a drug with body tissue can significantly improve the clinical performance of many agents used for treating oral disorders. These improvements range from better treatment of local pathologies to improved drug bioavailability and controlled release to enhanced patient compliance. There are abundant examples in the literature over the past 15 years of these improvements using bioadhesive polymers. This manuscript summarizes the innovations pertaining to formulation and treatments as described in recent patents.

Innovations in Coating Technology

Abstract: Despite representing one of the oldest pharmaceutical techniques, coating of dosage forms is still frequently used in pharmaceutical manufacturing. The aims of coating range from simply masking the taste or odour of drugs to the sophisticated controlling of site and rate of drug release. The high expectations for different coating technologies have required great efforts regarding the development of reproducible and controllable production processes. Basically, improvements in coating methods have focused on particle movement, spraying systems, and air and energy transport. Thereby, homogeneous distribution of coating material and increased drying efficiency should be accomplished in order to achieve high end product quality. Moreover, given the claim of the FDA to design the end product quality already during the manufacturing process (Quality by Design), the development of analytical methods for the analysis, management and control of coating processes has attracted special attention during recent years. The present review focuses on recent patents claiming improvements in pharmaceutical coating technology and intends to first familiarize the reader with the available procedures and to subsequently explain the application of different analytical tools. Aiming to structure this comprehensive field, coating technologies are primarily divided into pan and fluidized bed coating methods. Regarding pan coating procedures, pans rotating around inclined, horizontal and vertical axes are reviewed separately. On the other hand, fluidized bed technologies are subdivided into those involving fluidized and spouted beds. Then, continuous processing techniques and improvements in spraying systems are discussed in dedicated chapters. Finally, currently used analytical methods for the understanding and management of coating processes are reviewed in detail in the last section of the review.

Emerging role of microemulsions in cosmetics.

Abstract: Microemulsions represent a promising carrier system for cosmetic active ingredients due to their numerous advantages over the existing conventional formulations. They are capable of solubilizing both hydrophilic and lipophilic ingredients with relatively higher encapsulation. There is growing recognition of their potential benefits in the field of cosmetic science in addition to the drug delivery. They are now being widely investigated for preparing personal care products with superior features such as having improved product efficiency, stability or appearance. They are well suited for the preparation of various cosmetic products for use as moisturizing and soothing agents, as sunscreens, as antiperspirants and as body cleansing agents. They are also valuable for use in hair care compositions which ensure a good conditioning of the hair as well as good hair feel and hair gloss. They have also found application in after shave formulations which upon application to the skin provide reduced stinging and irritation and a comforting effect without tackiness. These newer formulations elicit very good cosmetic attributes and high hydration properties with rapid cutaneous penetration which may accentuate their role in topical products. These smart systems are also suitable for perfuming purposes where minimum amount of organic solvents is required, such as for perfuming skin or hair. This article highlights the recent innovations in the field of microemulsion technology as claimed by different patents which can bring unique products with great commercial prospects in a very competitive and lucrative global cosmetic market.

Liposomal formulation for dermal and transdermal drug delivery: past, present and future.

Abstract: Although the formulation of effective topical drug delivery system is one of the most sophisticated pharmaceutical preparations, it has attracted researchers due to many medical advantages associated with it. Topical drug delivery systems can act superficially on skin surface, locally in dermal layer of the skin or transdermally to provide successful delivery of drug molecules to the systemic circulation avoiding the traditional problems and limitations of conventional routes of drug delivery. Many novel formulations have been utilized topically to enhance either permeability or drug targeting to a specific layer of the skin such as Liposomes, ethosomes, transfersomes, niosomes and catezomes. The main problem with all of these formulations is that there is no distinct barrier between the targeting and localization action to a certain layer of the skin and the transdermal action to the circulation of these preparations. Any minimal change in the formulation could transform it from a local targeting preparation to a systemic one. This article deals with the innovations pertaining to the use of various types of liposomal preparations and liposomal like preparations for topical drug delivery and the patents associated with it.

Recent patents on ocular drug delivery systems

Abstract: There are three main routes for delivery of drugs to the eye: topical, systemic and intra-ocular injection. Controlled delivery systems, such as ocular inserts, minitablets and disposable lenses, can be applied to the exterior surface of the eye for treatment of conditions affecting the anterior segment of the eye. Extended residence times following topical application have the potential to improve bioavailability of the administered drug and additionally a range of strategies has been tested to improve penetration including cyclodextrins, liposomes and nanoparticles. The first part of this review will focus on recent patent filings in this area. The second part of the review reports on drug delivery strategies for treatment of diseases of the posterior segment of the eye. The development of therapeutic agents that require repeated, long-term administration is a driver for the development of sustained-release drug delivery systems to result in less frequent dosing and less invasive techniques. This review article focuses on recently patented applications (from March 2004 to present) of drug delivery systems for ocular delivery.

Intra-articular drug delivery: a fast growing approach

Abstract: Joint diseases are a leading cause of pain and disability in the adult population. Attempts have been made over the years to alleviate the pain accompanying these diseases and to decrease the incidence of joint degeneration. The utilization of the intra-articular route for the delivery of drugs and other macromolecules has recently evolved making use of the avascularity of the cartilage tissue to allow regional administration of the drug within the joint space rather than the systemic circulation. Several delivery systems such as hyaluronic acid systems, microparticles, nanoparticles, hydrogels, and thermoreversible systems have been developed in order to allow sustained drug delivery in the vicinity of the joint and to achieve high drug concentrations at the site of action. This review article focuses on the patented applications related to intraarticular delivery and sheds more light on current work involving this unique route.

Buccoadhesive drug delivery systems--extensive review on recent patents.

Abstract: Peroral administration of drugs, although most preferred by both clinicians and patients has several disadvantages such as hepatic first pass metabolism and enzymatic degradation within the GI tract, that prohibit oral administration of certain classes of drugs especially peptides and proteins. Consequently, other absorptive mucosae are considered as potential sites for administration of these drugs. Among the various transmucosal routes studied the buccal mucosa offers several advantages for controlled drug delivery for extended period of time. The mucosa is well supplied with both vascular and lymphatic drainage and first-pass metabolism in the liver and pre-systemic elimination in the gastrointestinal tract is avoided. The area is well suited for a retentive device and appears to be acceptable to the patient. With the right dosage form, design and formulation, the permeability and the local environment of the mucosa can be controlled and manipulated in order to accommodate drug permeation. Buccal drug delivery is thus a promising area for continued research with the aim of systemic and local delivery of orally inefficient drugs as well as feasible and attractive alternative for non-invasive delivery of potent protein and peptide drug molecules. Extensive review pertaining specifically to the patents relating to buccal drug delivery is currently available. However, many patents e.g. US patents 6, 585,997; US20030059376A1 etc. have been mentioned in few articles. It is the objective of this article to extensively review buccal drug delivery by discussing the recent patents available. Buccal dosage forms will also be reviewed with an emphasis on bioadhesive polymeric based delivery systems.

Inventions Designed to Enhance Drug Delivery Across Epithelial and Endothelial Cells Through the Paracellular Pathway

Abstract: Epithelia in multicellular organisms constitute the frontier with the environment. Hence, epithelial cells are specialized in regulating the transit of ions and molecules from and into the organism. Therapeutic agents in order to reach their targets frequently need to cross epithelial sheets. Two routes are available for such purpose: the transcellular and the paracellular pathways. The former is employed by lipophilic drugs and by molecules selectively transported by channels, pumps and carriers present in the plasma membrane. Hydrophilic molecules cannot cross biological membranes. Therefore their transepithelial transport is significantly enhanced if they move through the paracellular pathway. Transit through this route is regulated by tight junctions (TJs). This review focuses on patented inventions designed to open the paracellular route in a reversible manner in order to enhance drug delivery across epithelial and endothelial barriers. In these patents, the paracellular route is opened by altering the TJ with peptides homologous to the external loops of integral proteins of the TJ, antisense oligonucleotides and siRNA for TJ proteins, toxins and proteins derived from microorganisms that target TJ proteins, and with other molecules such as peptides, lipids, heparins, chitosan derivatives, phospholipase inhibitors and kinase activators.

A review of patent literature for iontophoretic delivery and devices.

Abstract: Skin forms a protective barrier to the entry of foreign molecules, especially water soluble compounds. Iontophoresis, one of the promising approaches to deliver water soluble drugs through the skin, has already been approved by FDA to deliver lidocaine and fentanyl. Iontophoresis involves application of current (< 0.5 mA/cm(2)) to push charged molecules into, or across the body tissue and offers programmable delivery. This technique encompasses various fields such as developing a device, sophistication of the device, electrode design, electronics and formulation. In addition, combination strategies with other enhancement techniques, is also gaining importance. The focus of this review is on the latest developments in the field of iontophoresis including trends in device development, electrode design, formulation and therapeutic applications as described in the patent literature.

On the use of hydrogels in cell encapsulation and tissue engineering system.

Abstract: Regenerative medicine requires the coordinated rebuilding of tissue and preservation of normal physiologic function. Cellular therapy incorporating tissue engineering principals has been among the most effective therapies, due to specific interactions between materials, cells, factors, and ligands that have been delineated over the last 5 decades. The current generation of these modalities incorporates the ability to control integration in vivo in a time- and space-dependent fashion. Hydrogels have been used as biofunctional vehicles for the introduction of these cell-based systems, and new techniques allow for the control of cell adhesion, proliferation, differentiation, and other biologic functions in vivo. With these more robust methods in place, and the ability to scale up and manufacture clinical materials, additional innovations have evolved that allow for ectopic or orthotopic administration of cellular therapies to treat disorders that have previously seen limited therapeutic promise due to inability to provide time-matched therapy. As such, critical discoveries have gained a unique niche portfolio of novel patents, accounting for a large portion of those newly filed in the field of biotechnology. These include the novel hydrogel compositions engineered by David Mooney and his colleagues, various tissue bulking and reconstructive applications invented by Hubbell and others, and other important patents in this field. The inventions described here provide insight into important aspects of this overall movement, and demonstrate significant immediate clinical utility in a variety of indications.

Dental Therapeutic Systems

Abstract: The recognition of periodontal diseases as amenable to local antibiotherapy has resulted in a paradigmatic shift in treatment modalities of dental afflictions. Moreover the presence of antimicrobial resistance, surfacing of untoward reactions owing to systemic consumption of antibiotics has further advocated the use of local delivery of physiologically active substances into the periodontal pocket. While antimicrobials polymerized into acrylic strips, incorporated into biodegradable collagen and hollow permeable cellulose acetate fibers, multiparticulate systems, bio-absorbable dental materials, biodegradable gels/ointments, injectables, mucoadhesive microcapsules and nanospheres will be more amenable for direct placement into the periodontal pockets the lozenges, buccoadhesive tablets, discs or gels could be effectively used to mitigate the overall gingival inflammation. Whilst effecting controlled local delivery of a few milligram of an antibacterial agent within the gingival crevicular fluid for a longer period of time, maintaining therapeutic concentrations such delivery devices will circumvent all adverse effects to non- oral sites. Since the pioneering efforts of Goodson and Lindhe in 1989, delivery at gingival and subgingival sites has witnessed a considerable progress. The interest in locally active systems is evident from the patents being filed and granted. The present article shall dwell in reviewing the recent approaches being proffered in the field. Patents as by Shefer, et al. US patent, 6589562 dealing with multicomponent biodegradable bioadhesive controlled release system for oral care products, Lee, et al. 2001, US patent 6193994, encompassing a locally administrable, biodegradable and sustained-release pharmaceutical composition for periodontitis and process for preparation thereof and method of treating periodontal disease as suggested by Basara in 2004via US patent 6830757, shall be the types of intellectual property reviewed and presented in the current manuscript.

Enhancing Transdermal Drug Delivery with Electroporation

Abstract: The application of electroporation to enhance transdermal delivery has opened up a new possibility to introduce larger molecules such as peptide hormones and vaccines as well as minigenes and RNAi etc. through the transdermal route. Many devices have been developed to deliver the pulse electric field needed to permeate the skin. These devices include both non-puncturing surface electrodes as well as puncturing electrodes of different geometrical arrangements. The latter type uses electroporation only to increase uptake of molecules injected through the puncturing electrode or syringe. Different electroporation protocols have been developed to maximize transport, uptake and minimizing pain. Synergistic effect of chemical enhancers and physical (sonic, vibrational and thermal) treatments are used to enhance the transport. This article reviews the patents pertaining to the instrumentation as well as application protocols of transdermal delivery, uptake enhancement and interstitial fluid sampling by electroporation.

Potential of nanocarriers in genetic immunization.

Abstract: DNA vaccination (or genetic immunization) strategies provide important opportunities for improving immunization, since both humoral and cell-mediated responses are induced. The use of genetic vaccines for inducing immunity to infectious agents can eliminate or significantly alleviate the pathology associated with a broad range of infections. A requirement for efficient DNA vaccination is the development of gene delivery systems capable of overcoming barriers to gene transfection. Compared to viral systems, nonviral systems are considered to be safe, cheap, multiple delivery is possible and able to deliver larger pieces of DNA. Also, these nanocarriers avoid DNA degradation and facilitate targeted delivery to antigen presenting cells. This review describes the potential of non-viral nanocarrier construct(s) in genetic immunization. Issued patents in the field were retrieved from the US patent database. Various carrier systems used to deliver plasmid DNA were reviewed in detail.

Potential of Microemulsions in Drug Delivery and Therapeutics: A Patent Review

Abstract: The recent success of cyclosporin marketed formulation - Sandimmune Neoral® by Sandoz in Europe has invigorated the gaining interest in microemulsions as potential drug delivery systems. These thermodynamically stable, transparent (or translucent) dispersions of oil and water stabilized by an interfacial film of surfactant molecules have potential applications whenever it is necessary to mix oil and water and where a large oil-water interface is required. Thus, microemulsions have drawn considerable interest. Until now excellent reviews covering aspects of bioavailability, theories, physical properties, formulation design, physical characterization, drug release and delivery potential have been cited in literature but there is no review that discusses the intellectual (patent) aspect of these delivery systems. In order to appreciate the intellectual potential of these delivery systems, this review summarizes the patents governing various applications of these delivery systems.

Incorporation of small molecular weight active agents into polymeric components.

Abstract: The incorporation of small molecular weight active agents into polymeric matrixes bearing controlled release characteristics represents an interesting strategy with numerous useful applications. Antimicrobials, biocides, fungicides or drugs, encapsulated into erodible or non-erodible polymeric micro-spheres, micro-capsules and micro-shells or/and embedded into continuous polymeric matrixes, are controlled released either by particular degradation routes or/and by specific stimuli. Cross-linking, curing or micro-porosity generating agents acting during polymerization impart additional controlled encapsulation characteristics to the active substances. Release modulating agents, like retardants or carrier materials used as vehicles are often encapsulated into microspheres or dispersed within polymeric compositions for the controlled introduction of an active agent into a liquid-based medium. The aim of this review is to reveal relevant strategies reported in recent patents on the encapsulation or incorporation of low molecular weight active agents into the matrix of polymers bearing controlled release characteristics. The inventions described implicate the formation of both erodible and non erodible polymer microparticles that contain active ingredients. Modification of polymer matrix and inorganic porous carriers represent pertinent major strategies that have been also developed and patented.

Patents on nanoparticulate drug delivery systems--a review.

Abstract: For the past few decades, there has been a considerable research interest in the area of drug delivery using particulate delivery systems as carriers for bioactive agents. Until now several reviews have been compiled on the nanoparticulate system concentrating on the various research works but there is no review, which compiles patents available for the nanoparticulate systems. Particulate systems like nanoparticles have been used as a physical approach to alter and improve the pharmacokinetic and pharmacodynamic properties of various types of drug molecules. A review on patents related to the nanoparticulate drug delivery systems has been prepared to summarize patents reported for the methods of preparation, applications in therapies and drug delivery. The status of patents for oral, topical and parenteral delivery has been discussed and the commercialized technology of nanoparticles for medical application has also been compiled.

Recent advances on patents in poly(ethylene glycol)-based drug delivery.

Abstract: Taking advantage of the peculiar features of poly(ethylene glycol), a wide range of applications in the field of drug delivery has been devised. In these last years, a series of patents have been applied on the use of this polymer in delivering of biopolymers, as peptides, proteins and nucleic acid derivatives, as well as of low molecular weight drugs. Moreover, several related strategies have been outlined for the modification of biocompatible materials employed in the field of drug delivery. In this review we focused our attention on the patents appeared in the last years; the description is not exhaustive but the reported citations have been selected as examples of the aforementioned applications.

Recent U.S. patents on protein drug formulation: 2000-2007.

Abstract: This review summarizes U.S. patents on protein drug formulation issued during the period 2000-2007. The patents fall into four major areas: (i) protein stabilization in solution and solid formulations, (ii) polymer-conjugated and chemically modified proteins, (iii) controlled release protein formulations, and (iv) protein formulation for novel routes of administration. Patents issued in each of the four areas are described and possible areas for additional research are noted.