Recent Patents on Drug Delivery & Formulation (v.8, #3)

It has been documented that telomere-associated cellular senescence may contribute to certain age-related disorders,including an increase in cancer incidence, wrinkling and diminished skin elasticity, atherosclerosis, osteoporosis,weight loss, age-related cataract, glaucoma and others. Shorter telomere length in leukocytes was associated crosssectionallywith cardiovascular disorders and their risk factors, including pulse pressure and vascular aging, obesity, vasculardementia, diabetes, coronary artery disease, myocardial infarction (although not in all studies), cellular turnover andexposure to oxidative and inflammatory damage in chronic obstructive pulmonary disease.;It has been proposed that telomere length may not be a strong biomarker of survival in older individuals, but it may be aninformative biomarker of healthy aging.;The data reveal that telomere dynamics and changes in telomerase activity are consistent elements of cellular alterationsassociated with changes in proliferative state and in this article these processes are consequently considered as the newtherapeutic drug targets for physiological control with advanced drug delivery and nutritional formulations. In particular,the presence of highly specific correlations and early causal relationships between telomere loss in the absence of telomeraseactivity and replicative senescence or crisis, and from the other side, telomerase reactivation and cell immortality,point to new and important treatment strategies or the therapeutic manipulation during treatment of age related disordersand cancer. Once better controls and therapeutic treatments for aging and age-related disorders are achieved, cellular rejuvenationby manipulating telomeres and enzyme telomerase activity may reduce some of the physiological declines thataccompany aging.;In this work, we raise and support a therapeutic concept of using non-hydrolyzed forms of naturally occurring imidazoledipeptidebased compounds carnosine and carcinine, making it clinically possible that slowing down the rate of telomereshortening could slow down the human aging process in specific tissues where proliferative senescence is known to occurwith the demonstrated evidence of telomere shortening appeared to be a hallmark of oxidative stress and disease.;The preliminary longitudinal studies of elderly individuals suggest that longer telomeres are associated with better survivaland an advanced oral nutritional support with non-hydrolyzed carnosine (or carcinine and patented compositionsthereof) and patented N-acetylcarnosine lubricant eye drops are useful therapeutic tools of a critical telomere length maintenancethat may fundamentally be applied in the treatment of age-related sight-threatening eye disorders, prolong life expectancy,increase survival and chronological age of an organism in health control, smoking behavior and disease.

Recent Patents on Ophthalmic Nanoformulations and Therapeutic Implications by Ann-Marie Ako-Adounvo, Ramesh C. Nagarwal, Lais Oliveira, Sai H.S. Boddu, Xiang S. Wang, Surajit Dey, Pradeep K. Karla (193-201).
Nanoformulations (NF) are widely explored as potential alternatives for traditional ophthalmic formulation approaches.The effective treatment of ocular diseases using conventional eye drops is often hampered by factors such as:physiological barriers, rapid elimination, protein binding, and enzymatic drug degradation. Combined, these factors areknown to contribute to reduced ocular residence time and poor bioavailability. Recent research studies demonstrated thatNF can significantly enhance the therapeutic efficacy and bioavailability of ocular drugs, compared to the established ophthalmicdrug delivery strategies. The research studies resulted in a number of patent inventions, reporting a significant increasein therapeutic efficacy for various chronic ocular disease states of both the anterior and posterior ocular segments.This article reviews these patent disclosures in detail and emphasizes the therapeutic advantages conferred by the followingnanoformulation approaches: Calcium Phosphate (CaP) nanoparticles, Liposomes, Nanoemulsions, Nanomicelles, andHydrogels. The nanoformulation approaches were shown to enhance the ocular bioavailability by reducing the drugproteinbinding, increasing the corneal resident time, enhancing the drug permeability and providing a sustained drug release.Further, the article discusses United States Food and Drug Administration (USFDA) approved ocular drugs employingnanotechnology and future developments.;It should be noted that, despite the potential therapeutic promise demonstrated by nanotechnology for ocular drug delivery,the bench to bed transition from patent inventions to marketed drug products has been insignificant. Majority of thediscussed technologies are still in development and testing phase for commercial viability. Further, studies are in progressto assess ocular tolerance and nanotoxicity for prolonged use of NF.

Recent Patents on Oral Insulin Delivery by Somnath D. Navgire, Amit S. Satpute, Suneel Pandey, Arun T. Patil (202-205).
Oral administration of Insulin, however, is extremely difficult due to its extremely low bioavailability. Developmentof oral Insulin formulations requires overcoming obstacles, such as low permeability of large molecules, lack oflipophilicity, and inactivation or rapid enzymatic degradation in the gastrointestinal (GI) tract.;The successful oral delivery of Insulin involves overcoming the barrier of enzymatic degradation, achieving epithelialpermeability, and conserving the bioactivity of the drug during formulation processing. Strategies proposed to maximizeoral Insulin bioavailability in Insulin delivery systems, to overcome barriers, and to develop safe and effective therapies,by using specific excipients, such as absorption enhancers, enzyme inhibitors, and mucoadhesive polymers, and usingcomposition allowing protection of Insulin from the harsh environment in the GI tract.;The present review includes study of patents on oral Insulin delivery. All the patents in the present review are arrangedand interconnected in such a way to improve viewer's knowledge at a glance. The comparative comments and discussionson the entitled topic make it easier to understand.

Patent Perspectives for Corticosteroids Based Ophthalmic Therapeutics by Preeti K. Suresh, Abhishek K. Sah (206-223).
Eye inflammation, if untreated at right time poses the risk of vision loss. Several categories of drugs are availablein the global market, but corticosteroids are still used for the treatment of ocular inflammation including anterior/posterior uveitis, age related macular degeneration (AMD) and post cataract surgery inflammation. Although corticosteroidshave well-documented side effects as compared to non steroidal anti-inflammatory drugs (NSAIDs), but they arestill regarded as better anti-inflammatory agents for treating ocular inflammations. The prime concern with conventionalformulations such as (ophthalmic solutions, suspensions, ointments) is low drug bioavailability due to precorneal barrierof the eye, tear turnover and rapid drainage of drug via nasolacrimal drainage and drug induced systemic toxicity. Toovercome these limitations, various novel formulations of corticosteroids have been explored. These include nanoparticles,solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), nanomicelles, in-situ gels, iontophoresis, liposomes,nanoemulsions, microemulsions and ocular implants for the effective ophthalmic delivery of the corticosteroids. Topicalnanocarriers have also been demonstrated to be promising vectors with potential application in the ophthalmic therapeutics.This review summarizes the clinical findings and patents on various corticosteroids as ocular pharmacotherapeutics.

New Mucoadhesive Polymeric Film for Ophthalmic Administration of Acetazolamide by Luis I. Tartara, Santiago D. Palma, Daniel Allemandi, Maria I. Ahumada, Juan M. Llabot (224-232).
This article reports the results concerning the design and manufacture of a novel polymeric film for ocular administrationof acetazolamide (AZM), and a patent document presented to INPI- National Institute of Industrial/IntelectualProperty. The system was designed using mucoadhesive polymers, such as carbomer (CB974P) and sodium carboxymethylcellulose(NaCMC), combined with the poloxamer (POL407) which behaves as a swelling modulator, surfactantand slightly plasticizer. The maximum amount of AZM to be incorporated without loss of homogeneity or precipitationof the drug, was 0.04 mg AZM/mg of the film. The addition of a polymeric coating based on Eudragit RSPO (cationicpermeable polymethacrylate polymer) allowed optimizing drug release. The coating in a proportion of 10% (determinedas percentage of total weight of the film) seemed to be the most adequate, since 80% of controlled drug release wasachieved along 240 minutes. This coating membrane did not affect the mucoadhesive properties of the swellable polymers.Thus, the system obtained, showed good efficiency and the intra ocular pressure (IOP) decreased according to theresults derived from in vivo studies performed on normotensive rabbits. Finally, irritation scored studies demonstrated thatthese systems were not irritant for rabbit's ocular mucosa.

Recent Patents Survey on Self Emulsifying Drug Delivery System by Sahilhusen I. Jethara, Alpesh D. Patel, Mukesh R. Patel (233-243).
Self-Emulsifying Drug Delivery System is a unique feasible approach to overcome low oral bioavailabilityproblem which is associated with the hydrophobic drugs due to their unparalleled potential as a drug delivery with thebroad range of application. The estimated 40% of active pharmaceuticals are poorly water soluble. Now recently, formulationcontaining oral SEDDS has received much interest as it solve problems related to oral bioavailability, intraand inter-subject variability and lack of dose proportionality of hydrophobic drugs. Now a days, it is the first way toinvestigate the development of any kind of innovative dosage forms. Many important in-vitro characteristics such assurfactant concentration, oil/surfactant ratio, emulsion polarity, droplet size and zeta potential play an important role inoral absorption of drug from SEEDS. It can be orally administered in the form of SGC or HGC and also enhancesbioavailability of drugs to increase solubility and minimizes the gastric irritation. After administration the drug remainsentrapped in the oily droplets (inside the droplet or in the surfactant`s film at the interface) of the emulsion thatare formed in the GIT upon self-emulsification process. It is also a bit problematic to say that the drug is being releasedfrom SMEDDS, it would be more precise to say that it diffuses out of oily droplets into the GIT media resultingin the formation of an equilibrium between the drug dissolved in oily droplets and the outer dispersed media (e.g. GITfluids). Many of the application and preparation methods of SEDDS are reported by research articles and patents indifferent countries. We present an exhaustive and updated account of numerous literature reports and more than 150patents published on SEDDS in the recent period. This current patent review is useful in knowledge of SEDDS for itspreparations and patents in different countries with emphasis on their formulation, characterization and systematic optimizationstrategies, thus paving the way for accelerated progress into the SEDDS application in pharmaceutical researchas well as patents on SEDDS methods.

Patent Selections (244-246).