Recent Patents on Drug Delivery & Formulation (v.9, #2)

Risk Assessment of Nanoformulations by Hemanta K. Sharma (106-106).

Recently, great attention has been paid to in situ gel-forming chitosan/glycerophosphate (CS/Gp) formulation due to its high biocompatibility with incorporated cells and medical agents, biodegradability and sharp thermosensitive gelation. CS/Gp is in liquid state at room temperature and after minimally invasive administration into the desired tissue, it forms a solid-like gel as a response to temperature increase. The overview of various recently patented strategies on injectable delivery systems indicates the significance of this formulation in biomedical applications. This thermosensitive hydrogel has a great potential as scaffold material in tissue engineering, due to its good biocompatibility, minimal immune reaction, high antibacterial nature, good adhesion to cells and the ability to be molded in various geometries. Moreover, CS/Gp hydrogel has been utilized as a smart drug delivery system to increase patient compliance by maintaining the drug level in the therapeutic window for a long time while avoiding the need for frequent injections of the therapeutic agent. This review paper highlights the recent patents and investigations on different formulations of CS/Gp hydrogels as tissue engineering scaffolds and carriers for therapeutic agents. Additionally, the dominant mechanism of sol-gel transition in those systems as well as their physicochemical properties and biocompatibility are discussed in detail.

By the virtue of their nature, cosmetic products are used to clean, perfume, change the appearance of the human body's various external parts and maintain them in a good condition. Their main sites of action may be exemplified by the nails, the hair system, the epidermis, the external genital organs and the mucous membranes of the oral cavity.
Sunscreen preparations consist of organic chemicals and inorganic materials. Inorganic materials include chemicals that scatter UV light physically like TiO2 and ZnO. Organic materials such as avobenzone reduce the amount of UV light to which the human skin is exposed by absorbing the radiation and subsequent disposal in different ways. One of the way of disposal may be by undergoing photoinduced decompositions which not only cause a reduction of the sunscreen UV-protective capacity during usage but may precipitate allergic or toxic degradates. Thus undoubtedly a high photostability is an important requirement for the effectiveness of sunscreen products.
Many researchers patented their work on this aspect of protection of avobenzone from photodegradation using varying methodologies.
This review article discusses some of the patented works done in enhancing the photostability of avobenzone and its formulations.

Advances in Patents Related to Intrapocket Technology for the Management of Periodontitis by Sarita K. Yadav, Gayasuddin Khan, Brahmeshwar Mishra (129-145).
Increased prevalence of oral diseases such as gingivitis, periodontitis and dental caries has become major health issue worldwide. Such growing incidence of periodontitis has directly affected the development of drug delivery systems and growth of the market. Since the infections are limited to periodontal pockets or oral cavity, localized intrapocket drug delivery will be more beneficial than conventional systemic administration. Advances in intrapocket technology and innovations in the field of periodontal drug delivery led to increased patent applications. Newer trends like use of mucoadhesive polymers, in situ forming gels, viscosity modifiers, plasticizers etc which can enhance intrapocket retention of drugs have gained considerable attention among researchers and industrialists. Current market is flooded with products such as Periostat, Periochip®, Atridox®, Arestin®, Actisite®, Dentomycin®, and Elyzol® and generics such as metronidazole, levofloxacin, tetracycline, doxycyline and minocycline for intrapocket delivery. There is a need of novel drugs and delivery systems with better efficacy profiles than the existing compounds. Inclusion of novel technologies like films, fibers, in situ forming implants, microparticles, nanoparticles, and liposomes as intrapocket drug delivery has great potential. Development of antibiotic free drug delivery such as antiseptics, host modulators, biofilms inhibitors and antibodies has promising role in the improvement of pathogenesis of periodontitis. Further, this review deals with various innovations in drug delivery and patents related to localized intrapocket administration of medicaments in the implications of periodontitis.

Review of Patents for Microneedle Application Devices Allowing Fluid Injections Through the Skin by Marion S. Lhernould, Serge Tailler, Michel Deleers, Alain Delchambre (146-157).
Microneedles have been developed in the past few years as a new means of transdermal drug delivery. They indeed present many advantages compared to injections using hypodermic needles (reduced risk of contamination and epidermic reactions), but mostly bring comfort and compliance to patients. Microneedles may be plain, opening pathways for medications to dissolve into the skin, or hollow, allowing fluid to actually enter the dermis or the hypodermis. This review focuses on the latter type of microneedles and two issues with their application: first, ensuring correct insertion into the skin (controlled and repeatable insertion depth, mainly); and second, ensuring correct fluid delivery to the dermis (controlled infusion rate). This paper thus focuses on recently published patents for hollow microneedle applicators-i.e., microneedles applicators that allow fluid delivery to the skin. Descriptions are given of several of the most relevant patents concerning this. The benefits and drawbacks of the different solutions are also described.

Increasing Neurogenesis with Fluoxetine, Simvastatin and Ascorbic Acid Leads to Functional Recovery in Ischemic Stroke by Adrian M. Corbett, Scott Sieber, Nicholas Wyatt, Jenna Lizzi, Tiffany Flannery, Bethany Sibbit, Saagar Sanghvi (158-166).
Less than 8.5% of ischemic stroke patients receive clot-busting drugs within the narrow time needed to reduce injury. Thus, there is need for an easily-accessible delayed post-stroke drug treatment to improve functional recovery. Various combinations of fluoxetine, simvastatin, and ascorbic acid were given to healthy rats to assess impact on neurogenesis versus controls. Fluoxetine combined with simvastatin and ascorbic acid produced a 19-fold increase in neurogenesis versus controls in healthy rats; fluoxetine alone produced 10-fold increase.
We next tried a couple of drug combinations versus control in endothelin-induced stroked rats. Combined fluoxetine/ simvastatin/ascorbic acid treatment, given to stroked rats 20-26 hours after stroke induction and continued for 31 days, produced strong recovery as measured by Montoya staircase test (mean recovery to 85% of pre-stroke function) and Forelimb Asymmetry test (mean recovery to 90% of pre-stroke function). Fluoxetine and ascorbic acid without simvastatin only produced ~50% of recovery produced by the 3-drug combination.
Our results indicate that combined treatment of Fluoxetine, simvastatin and ascorbic acid represents a promising delayed stroke treatment that greatly improves functional recovery in rats and warrants further study in human patient populations. This work formed the basis for a patent submission (US20130065924A1) Composition and method for treatment of neurodegeneration.

Objective: Norfloxacin has a low aqueous solubility which leads to poor dissolution. Keeping this fact in mind the purpose of the present study is to formulate and evaluate norfloxacin solid dispersion. Methods: Solid dispersions were prepared using hydrophilic carriers like polyethylene glycol (PEG) 4000, polyvinylpyrrolidone (PVP) k30 and carbopol 974pNF (CP) in various ratios using solvent evaporation technique. These formulations were evaluated using solubility studies, dissolution studies; Fourier transmitted infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetery (DSC). The influence of polymer type and drug to polymer ratio on the solubility and dissolution rate of norfloxacin was also evaluated. Results: FTIR analysis showed no interaction of all three polymers with norfloxacin. The results from XRD and DSC analyses of the solid dispersion preparations showed that norfloxacin existsin its amorphous form. Among the Norfloxacin: PEG solid dispersions, Norfloxacin: PEG 1:14 ratio showed the highest dissolution rate at pH 6.8. For norfloxacin: PVP solid dispersions, norfloxacin: PVP 1:10 ratio showed the highest dissolution rate at pH 6.8. For Norfloxacin: CP solid dispersions, norfloxacin: P 1:2 ratio showed the highest dissolution rate at pH 6.8. Conclusion: The solid dispersion of norfloxacin with polyethylene glycol (PEG) 4000, polyvinylpyrrolidone (PVP) k30 and carbopol 974p NF (CP), lends an ample credence for better therapeutic efficacy.

Patent Selections: (183-184).