Recent Patents on Drug Delivery & Formulation (v.9, #1)

Hypothalamic releasing and inhibiting hormones are major neuroendocrine regulators of human body metabolism being driven directly to the anterior pituitary gland via hypothalamic-hypophyseal portal veins. The alternative physiological or therapeutic interventions utilizing the pharmaco-nutritional boost of imidazole-containing dipeptides (non-hydrolized oral form of carnosine, carcinine, N-acetylcarnosine lubricant eye drops) can maintain health, enhance physical exercise performance and prevent ageing. Carnosine (β-alanyl-L-histidine) is synthesized in mammalian skeletal muscle. There is an evidence that the release of carnosine from the skeletal muscle sarcomeres moieties during physical exercise affects autonomic neurotransmission and physiological functions. Carnosine released from skeletal muscle during exercise acts as a powerful afferent physiological signaling stimulus for hypothalamus, may be transported into the hypothalamic tuberomammillary nucleus (TMN), specifically to TMN-histamine neurons and hydrolyzed herewith via activities of carnosine-degrading enzyme (carnosinase 2) localized in situ. Through the colocalized enzymatic activity of Histidine decarboxylase in the histaminergic neurons, the resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and physiological function.
Carnosine and its imidazole-containing dipeptide derivatives are renowned for their anti-aging, antioxidant, membrane protective, metal ion chelating, buffering, anti-glycation/ transglycating activities used to prevent and treat a spectrum of age-related and metabolic diseases, such as neurodegenerative disease, sight threatening eye diseases, Diabetes mellitus and its complications, cancers and other disorders due to their wide spectrum biological activities. The precursor of carnosine (and related imidazole containing compounds) synthesis in skeletal muscles beta-alanine is used as the oral supplement by athletes to achieve the fine sporting art results due to the buffering activities of carnosine and its related imidazole- containing compounds which contribute to the maintenance of the acid-base balance in the acting muscles. This work originally emphasizes that overall data indicate the signaling activities of carnosine in skeletal and cardiac muscles switching on the mechanisms of exercise-induced telomere protection and point to the stress response and growth/cellular proliferation pathways as high-priority candidates for the ongoing studies and therapeutic concepts. The therapeutic interventions utilizing the specific oral formulation (Can-C Plus), timing dosing and pharmaco-nutritional boost of imidazolecontaining dipeptides can maintain health, enhance physical exercise performance and prevent aging. The patented therapeutic concept protects the existence of the interesting physiological major activities, better controls and therapeutic treatments for aging/age-related disorders (including age-related loss of muscle mass and muscle function) using carnosine dipeptide for cellular rejuvenation and manipulating telomeres and enzyme telomerase activity that may reduce some of the physiological declines that accompany aging.

Recent Survey on Nanosuspension: A Patent Overview by Sahilhusen I. Jethara, Alpesh D. Patel, Mukesh R. Patel, Mukesh S. Patel, Kanu R. Patel (65-78).
The major goals of designing nanosuspension of nanosize materials are increasing due to their tremendous potential as a drug delivery system with the wide range of applications. Nanosuspension is a unique tool for improving the bioavailability of poorly soluble drugs. Nanosuspension drug delivery has wide range of application like oral, injectable, transdermal, inhalation, peroral, ocular, pulmonary and topical etc. by improviing the bioavailability, reducing the dose, gastric irritation, decreasing intra subject variability and increasing adhesivness with intestinal membrane. Recently, nanosuspension has been received much interest as a way to resolve solubility and stability problem because of their cost-effectiveness and technical simplicity compare to other liposome and colloidal drug carriers. Nanosuspensions are engaged to control particle size, surface properties and release of pharmacologically active agents in order to achieve the site-specific action of the drug at the therapeutically optimal rate, improve the bioavaibility of drug with poor solubility and dose regimen. Application and preparation method of nanosuspension has been reported by research articles and patented in different countries. Most of the marketed nanosuspensions are in preclinical and clinical based study for its application. More than 100 patents have been published on nanosuspensions by the recent days. This patent reviews covers different methods of pharmaceutical preparation and applications in drug delivery as well as the recent marketed published or granted patent surveys. This patent review is useful in enhance the knowledge of controlled drug delivery and applications.

An Overview of Recent Patents on Composition of Mucoadhesive Drug Delivery Systems by Marcos L. Bruschi, Lizziane M.B. de Francisco, Lucas de Alcantara. S. de Toledo, Fernanda B. Borghi (79-87).
Mucoadhesion began to be applied to therapeutic systems with the aim of the incorporation of bioadhesive molecules into pharmaceutical dosage forms intended to keep in close contact with the tissue, releasing the drug near the action site, thereby increasing its bioavailability and promoting local or systemic effects. Different mucoadhesive materials and dosage forms have been studied, since the properties of mucoadhesion largely depend on the features of the material used in its preparation. This mini-review focuses on mucoadhesive therapeutic systems, the main mucosal routes of administration, and materials used to prepare the systems over the last five years. Patents and applications were reviewed, categorized and the materials were described together with the proposed systems.

The present critical review is related to the self-modified patch based drug delivery system for controlled (trans) dermal drug delivery. The composition itself is modified into the patch and adheres when comes in contact with the skin and acts as a rate-controlling matrix layer (patch). The self adhesiveness property of the formulation itself is enough to hold the patch in place on the skin for the - duration of treatment while allowing the patch to be promptly backed by without any skin irritation and formulation residue. This patent review is useful for the knowledge of self modified patch associated drug delivery for controlled topical or transdermal delivery of pharmaceutical and cosmetic agents.

Formulation and Evaluation of Transdermal Patches of Donepezil by Jyotsana R. Madan, Nitin S. Argade, Kamal Dua (95-103).
Aims and Background: Donepezil (DNZ) is a centrally acting reversible acetyl cholinesterase inhibitor. The main therapeutic use of donepezil is in the treatment of Alzheimer's disease. The present research work pertains to the preparation of transdermal patches of donepezil with the objective to improve its patient compliance, therapeutic efficacy and to reduce the frequency of dosing and side effects as well as to avoid its extensive first pass metabolism. The recent patents on Rivastigmine (WO2013150542A2), Xanomeline (US5980933A) and Propentofylline (CA2255580A1) helped in selecting the drug and polymers. Materials and Methods: The transdermal patches were prepared using various polymers in combination with the plasticizer and penetration enhancers. The physicochemical parameters like folding endurance, thickness, drug content, content uniformity, moisture absorption, weight variation, and drug permeation studies of the optimized patches were studied. Results: The system containing Eudragit S -100, Eudragit E -100 and HPMC as matrix forming agent and glycerine as plasticizer was the best formulation. The in vitro release data was treated with kinetic equations and it followed zero order release. The diffusion study was carried out using rat skin showed 89% drug was released within 72 hours. Tween-80 (0.83 % w/w) was found to be the best among all penetration enhancers. All the transdermal patches had the desired physical properties like tensile strength, folding endurance, flatness and water vapor transmission rate etc. Conclusion: The study concluded that that transdermal patch can extend the release of donepezil for many hours and also ensure enhanced bioavailability, further it also helps in avoiding the first pass effect.

Patent Selections: (104-104).