Recent Patents on Drug Delivery and Formulation最新文献

The oral bioavailability enhancement of poorly water-soluble medicaments is still one of the most complicated aspects of the formulation development. Various approaches are currently available for solubility and rate of dissolution enhancement such as salt formation, solubilization and reduction of particle size, each with its own limitations and advantages. Solid dispersion is one of the most suitable approaches for the formulation development of poorly water-soluble drugs. The popularity of solid dispersion is evident from the increasing number of patent applications and patents granted in this field during recent years. This article reviews the various approaches for the preparation of solid dispersion such as a solvent melting, hot-melt extrusion method, solvent evaporation method, cryogenic processing approaches etc. from the perspective of patents filed or granted for these techniques. Some of the aspects taken into account before the preparation of solid dispersions are carrier selection and physicchemical testing along with an insight into the molecular arrangement of medicaments in solid dispersion. The manuscript further highlights various commercial patented technology platforms such as Solumertm, Hovione and Kinetisol which are based on the concept of solid dispersions.

Current Development in drug delivery system has been employed with an endeavour to enhance the bioavailability of the drug, mask its taste, induce the rapid onset of action and improve patient compliance. An alternative approach to the conventional dosage form is being employed to triumph over all these issues named as Orodispersible system. Over the past three decades, this novel dosage form has gained considerable attention as compared to other conventional solid dosage forms such as tablets and capsules. ODTs dissolve or disintegrate within a few seconds or a minute when put on the tongue, without the need for water. ODT has an advantageous effect on paediatrics and geriatrics patients with dysphagia. Over the last decade, widespread advances in the formulation of ODTs have been executed in academia and industry that resulted in the emergence of a large number of patents. Products developed from ODT mechanics launched in the market in the 1980s have grown bit by bit in demand and their products are rapidly escalating. Expanding in the technology forum based on industrialization, these systems include the use of lyophilization, cotton candy, sublimation, melt extrusion and direct compression in addition to the conventional wet granulation processes and patent techniques. The present study focused on non-patent and patent citations concerning ODT along with active ingredients, techniques used and results of the innovations.

Background: Dental caries originate due to the localized dissolution of the hard tissues of teeth, mainly caused by acids, developed by the presence of microorganisms in the biofilm (dental plaque) on the surface of teeth causing "cavities". Commercially available liquid mouthwashes containing synthetic active ingredients possess limitations like teeth staining, higher alcoholic content, taste disturbances, xerostomia, and stability issues.

Objective: To make the solid preparation for oral hygiene (US6428770B1) in the form of herbal effervescent mouthwash tablet (CN106619318A, US8728446B2) using Azadirachta indica and Curcumin having antimicrobial, antibacterial, antiplaque, and anti-inflammatory activity.

Methods: The optimization study of effervescent granules was performed by 33 factorial design. A total of 27 preliminary experimental batches were prepared by the fusion method, varying the amount of citric acid, tartaric acid, and sodium bicarbonate. A complex of curcumin was prepared with hydroxyl propyl β-cyclodextrin and further examined by scanning electron microscopy. The prepared tablets were evaluated for pre and post-compression parameters. The in vitro antimicrobial study was performed by Agar well diffusion method against S. mutans.

Results: All the experimental batches of effervescent granules were evaluated for pH, effervescent time, and CO2 content. Six batches were further selected for final tablet preparation. The results of the pre-compression parameters revealed excellent flow properties and post-compression parameters; the results were also significant. The antimicrobial study revealed the F3 as a final best formulation.

Conclusion: The developed herbal formulation (F3) has a good potential to maintain oral hygiene as compared to alcoholic mouthwash and further studies may be necessary to confirm the efficacy of the formulation since only a single bacterial strain was assayed.

Background: Cancer is a condition in which some cells in the body grow uncontrollably and can also spread in other parts of the body. Among males, oral and lung cancers account for 25 % cancer deaths, while in females, breast and oral cancers cause 25% death. Breast and cervical cancers are the underlying cause of the high mortality rate among women. Owing to limitations of conventional cancer therapy like low drug specificity, less solubility, multidrug resistance, poor access to tumor cells and low bioavailability development of environmentally sensitive and target specific nanocarriers are imperative.

Objective: The objective of this study is to review advancements made in techniques to synthesize Mesoporous Silica Nanoparticles (MSN's) as well as strategies to functionalize its silanol group for site-specific drug release in the tumor environment and to review recent patents published regarding it. To describe rationale for selection of MSN's for cancer theranostics amidst other nanocarriers developed.

Methods: In the first section of this review, the physical and chemical properties of MSNs making it an ideal delivery system for cancer therapy and diagnostics are discussed. In the next section, various techniques involved in synthesizing and loading MSNs, including the influence of basic components of MSNs and reaction conditions on its properties are reviewed. Then the wide application of MSNs and various exogenous and endogenous stimuli harnessed for site-specific delivery of cargo and recent patents on modifying environmental conditions for large scale synthesis of MSNs and its active targeting for cancer treatment and bioimaging are discussed.

Results: Physico-chemical properties and synthetic protocols of MSNs justifying them to be a promising nanovector to overcome the ill effects of traditional chemotherapy. The superlative attributes of MSNs including, tunable size, morphology, high load volume, stability, ease of modifying external and internal surface leverage applications in various dimensions of therapeutics, diagnostics, and combinatorial drug delivery. MSNs surface functionalization can be harnessed for passive and active targeting by either coating the surface with polymers or attaching various ligands.

Conclusion: An ideal nano-carrier must have high loading efficiency, easily detectable, and must have stimuli's sensitive, site-specific drug release. The patent study explores new dimensions on MSNs synthesis by claiming new cost-effective templates and silica source, a more safe environment for synthesis, reducing synthesis steps, duration of reaction, effective loading of low solubility drugs by magnetized nanocarriers, pathogen-specific release and development of novel photoluminescent rechargeable MSNs under mild conditions. It's a challenging task for researchers to successfully translate their prototypes to ind

Nanotechnology is one of the emerging fields in drug delivery for targeting the drug to the site of action. The polymeric nanoparticles as drug delivery systems have gained importance for the last few decades. They offer advantages over liposomes, dendrimers, emulsions etc. Surface engineering of polymeric nanoparticles is widely utilized to effectively target the cells in various diseases such as cancer, HIV infection. Surface modified nanoparticles offer various advantages such as targeted drug delivery, reduction in side effects, dose reduction and improved therapeutic efficacy. Moreover, they can aid in improving physical and biochemical properties, pharmacokinetic and pharmacodynamic profiles of the drug. Surface modified polymeric nanoparticles can provide targeted delivery of drugs into specific cells, especially when targets are intracellularly localized. This approach of surface modification would be more advantageous for the delivery of various anticancer, anti-inflammatory, anti-HIV drugs for more effective therapy. This review focuses on the techniques used for the fabrication of polymeric nanoparticles, the material used for surface modification and their applications.

Introduction: The purpose of this study was to determine if pharmacological treatment could increase progenitor cell proliferation in the Sub-ventricular Zone of aged rats. Previous work had shown that increasing progenitor cell proliferation in this region correlated well (R2=0.78; p= 0.0007) with functional recovery in a damaged corpus callosum (white matter tract), suggesting that progenitor cell proliferation results in oligodendrocytes in this region.

Methods: 10 month old male and female Sprague Dawley rats were fed the drugs for 30 days in cookie dough, then immunocytochemistry was performed on coronal brain sections, using Ki67 labeling to determine progenitor cell proliferation.

Results: Female rats showed low endogenous (control) progenitor cell proliferation, significantly different from male rats (P<0.0001), at this age. Ascorbic Acid (20 mg/kg, daily for 30 days) increased progenitor cell proliferation overall, but maintained the innate gender difference in stem cell proliferation (P=0.001). Prozac (5 mg/kg, daily for 30 days) increased progenitor cell proliferation for females but decreased stem cell proliferation for males, again showing a gender difference (P<0.0001). Simvastatin (1 mg/kg for 30 days) also increased progenitor cell proliferation in females and decreased progenitor cell proliferation in males, leading to a significant gender difference.

Discussion: The three drug combinations (fluoxetine, simvastatin, and ascorbic acid, patent # 9,254,281) led to ~ 4 fold increase in progenitor cell proliferation in females, while male progenitor cell proliferation was highest with 50 mg/kg ascorbic acid. However, the ascorbic acid increase in proliferation appears to be only on the sides of the ventricles, which is not the region that normally gives rise to oligodendrocytes.

Conclusion: There are innate gender differences in progenitor cell proliferation at the Sub-Ventricular Zone at middle age in rats, possibly due to the loss of estrogen in females. We also see notable gender differences in progenitor cell proliferation in the Sub ventricular Zone in response to common drugs, such as fluoxetine, simvastatin and Vitamin C (ascorbic acid).

Atopic dermatitis is a chronic inflammatory disease of the skin, which is characterized by itching, erythema, and eczematous lacerations. It affects about 10 % of adults and approximately 15-20 % of children worldwide. As a result of genetic, immunologic, and environmental factors, the disease manifests itself with the impaired stratum corneum barrier and then immunological responses. Topical administration of corticosteroids and calcineurin inhibitors are currently used as the first strategy in the management of the disease. However, they have low skin bioavailability and some side effects. The nanocarriers as novel drug delivery systems could overcome limitations of conventional dosage forms, owing to increment of poorly soluble drug' solubility, then its thermodynamic activity and, consequently, its skin permeation. Also, side effects of the drug substances on the skin could be reduced by the nano-sized drug delivery systems due to encapsulation of the drug in the nanocarriers and targeted drug delivery of drug substances to the inflammated skin areas. Thereby, there have been available numerous research studies and patents regarding the use of nanocarriers in the management of atopic dermatitis. This review focuses on the mechanism of disease and development of nanocarrier based on novel drug release systems in the management of atopic dermatitis.

Fast Dissolving/Disintegrating Dosage Forms (FDDFs) are a group of dosage forms which dissolve or disintegrate quickly, leading to fast distribution of active ingredients at the site of administration; thereby providing ease of oral ingestion of solid unit dosage forms and have the potential to enhance transmucosal absorption. With time, the use of FDDFs in alternative systems has significantly increased. Homeopathic systems and traditional Chinese medicine have embraced FDDFs for the delivery of active compounds. Most of the patents in this area are from China or by the Chinese innovators. In Europe and US, FDDFs have been extensively studied for the delivery of natural active compounds. It was fascinating to know that some new dosage forms and new routes of delivering active compounds are also making their way to the family of FDDFs. The dose of active compound, size of dosage forms, standardization of extracts, polyherbal mixtures, stability of active compounds, safety, efficacy and pharmacokinetics are challenging issues for developing FDDF herbal formulations or phytopharmaceuticals.

The traditional oral dosage forms (tablets, capsules, syrups, and elixirs) suffer from various disadvantages. They are pretty challenging to administer to patients with dysphagia, mucositis, and vomiting tendency. Therefore, gaining patient compliance using conventional dosage forms is highly cumbersome. One of the most transformative and innovative approaches to overcome such challenges is Orodispersible Films, a Novel Drug Delivery System. They are easy to consume, no need to chew or swallow and they do not even require water for consumption. Therefore, several drugs have been converted into orodispersible films to gain patient compliance. With the advent of these film formulations, new innovations are erupting and accordingly, companies in India are actively protecting them by filing ordinary patent applications in India and internationally under the Patent Cooperation Treaty. Patenting in India poses unique patentability challenges when compared with rest of the world. Nonetheless, meeting all the challenges and obtaining a valid patent not only help in recouping the cost involved in developing new drugs and its novel drug delivery systems but also helps in taking legal action against alleged infringers. This review article identifies key active Indian players in the domain of ODF based on their patent filings in India (and abroad) and also identifies the challenges they face to obtain a grant.