Recent Patents on Drug Delivery & Formulation (v.7, #3)

Lipid aggregates, mainly liposomes, have been used as drug carriers for quite some time. Recently, nonlamellarliquid crystalline lipid systems, such as inverted bicontinuous cubic, hexagonal and sponge mesophases, attract attentionas possible drug-delivery vehicles because of their unique microstructure and physicochemical properties. Various bioactivemolecules can be solubilized and protected from hydrolysis or oxidation in either the aqueous or the oil lipid phase.Nonlamellar liquid crystalline lipid aggregates have demonstrated high encapsulating capacity and ability for controlledrelease of drugs. Valuable properties such as a wide solubilization spectrum, high drug payloads, effective encapsulation,stabilization and protection of sensitive drug substances, define the nonlamellar lipid aggregates as promising pharmaceuticalcarriers. This review summarizes the recent patents on new formulations based on nonlamellar liquid crystalline lipidphases and their efficiency as drug carriers.

Delivery of medication to the neonatal lung using current methods is inefficient. Aerosols offer one way to improvedelivery to small airways. In this in vitro work, aerosol delivery by using a micropump or a rotary valve has beenevaluated in a model of the neonatal setting with a pressurised metered dose inhaler plus spacer outside of the inspiratorylimb. Drug depositions were assessed by spectrophotometric analyses. Drug lung deposition was increased by adjustingthe rotary valve for co-ordination between the inhalation and aerosol delivery, but this intermittent mode decreased theaerosol delivery by using the micropump. Also, decreasing the volume of spacer decreased drug deposition in test lungsby using the micropump system. At the optimum conditions, the rotary valve aerosol delivery system delivered3.68±0.91% of the Qvar nominal dose to the test lungs, and this was 2.34±0.01% for the micropump system. In conclusion,the rotary valve aerosol delivery system provided higher amounts of drug particles to the test lungs compared to themicropump system. The advantages of these methods were that the humidity in the ventilation circuit did not affect theaerosol particles in the spacer. Further optimisation is required to improve aerosol deposition in the test lungs. The articlehas also a short section of recent patents relevant to aerosol delivery.

Transdermal Delivery: Product and Patent Update by Himanshu Gupta, RJ Babu (184-205).
Transdermal drug delivery is an attractive alternative to the oral and parenteral drug delivery. Drugs which areprone to first-pass metabolism can be delivered easily in small doses with sustained blood levels through this method. Anupdate to available products along with a review of clinical trials and patents are discussed in this study. In this review, wehave compiled 16 drugs, i.e. Buprenorphine, Clonidine, Estradiol, Fentanyl, Granisetron, Lidocaine, Methylphenidate,Nicotine, Nitroglycerin, Oxybutynin, Rivastigmine, Rotigotine, Scopolamine, Selegiline, Testosterone, Influenza virusvaccine (Microneedle) and covering about 22 marketed products on the transdermal system. We present instrumentalinformation on them along with the compilation of current clinical trials on transdermal systems. We summarize thecontents of patents granted in last 5 years under different pharmacological categories. This article serves, accordingly as asource of available information focused on transdermal drug delivery research.

Recent Patents on Stimuli Responsive Hydrogel Drug Delivery System by Gayatri C. Patel, Chintan A. Dalwadi (206-215).
Hydrogels are cross-linked hydrophilic polymer structures that imbibe large quantities of water or biologicalfluids. Hydrogels are an upcoming class of polymer-based controlled release drug delivery systems, embracing numerousbiomedical and pharmaceutical applications. Hydrogels are swellable polymeric materials, and are being widely investigatedas a carrier for drug delivery systems. Besides exhibiting swelling-controlled drug release, hydrogels also showstimuli responsive changes in their structural network and hence leading to the drug release. The present manuscript isconcerned with the classification, method of preparation; application in drug deliveryand FDA approved market productsof hydrogels with the patent review on hydrogel composition and its manufacturing process. It also highlights recentadvances in hydrogel drug delivery especially stimuli-responsive hydrogel and its patents. This patent review is useful inthe synthesis methods of hydrogel drug delivery and its application.

Diabetes Mellitus: Novel Insights, Analysis and Interpretation of Pathophysiology and Complications Management with Imidazole-Containing Peptidomimetic Antioxidants by Mark A. Babizhayev, Vadim Z. Lankin, Ekaterina L. Savel'Yeva, Anatoliy I. Deyev, Yegor E. Yegorov (216-256).
Patients suffering from the severe complications associated with both insulin- (IDDM) and non-insulin-dependentdiabetes mellitus (NIDDM): nephropathy, retinopathy, neuropathy, and atherosclerosis are still largely left without a prospectof an efficient treatment. Chronic hyperglycaemia, the primary clinical manifestation of diabetes, is associated with developmentof certain of the diabetic complications. The accelerated formation of advanced glycation end-products (AGEs) due toelevated glycemia has repeatedly been reported as a central pathogenic factor in the development of diabetic microvascularcomplications. Glucose and α-dicarbonyl compounds chemically attach to proteins and nucleic acids without the aid of enzymes.Initially, chemically reversible Schiff base and Amadori product adducts form in proportion to glucose concentration.;The major biological effects of excessive nonenzymatic glycosylation are leading to increased free radical production andcompromised free radical inhibitory and scavenger systems, inactivation of enzymes; inhibition of regulatory moleculebinding; crosslinking of glycosylated proteins and trapping of soluble proteins by glycosylated extracellular matrix (bothmay progress in the absence of glucose); decreased susceptibility to proteolysis; abnormalities of nucleic acid function; alteredmacromolecular recognition and endocytosis; and increased immunogenicity.;The discovery of chemical agents that can inhibit deleterious glycation reactions is potentially of great therapeutic benefitto all diabetes-associated pathologies.;This study demonstrates the progress in development of patented carnosine mimetics resistant in formulations to enzymatichydrolysis with human carnosinases that are acting as a universal form of antioxidant, deglycating and transglycatingagents that inhibit sugar-mediated protein cross-linking, chelate or inactivate a number of transition metal ions (includingferrous and copper ions), possess lipid peroxidase type of activity and protection of antioxidant enzymes from inactivation(such as in a case of superoxide dismutase). Carnosine biological mimetics react with methylglyoxal and theyare described in this study as a glyoxalase mimetics. The imidazole-containing carnosine biological mimetics can reactwith a number of deleterious aldehydic products of lipid peroxidation and thereby suppress their toxicity. Carnosine andcarcinine can also react with glycated proteins and inhibit advanced glycation end product formation.;These studies indicate a therapeutic role for imidazole-containing antioxidants (non-hydrolized carnosine, carcinine,D-carnosine, ophthalmic prodrug N-acetylcarnosine, leucyl-histidylhidrazide and patented formulations thereof) intherapeutic management strategies for Type 2 Diabetes.

Patent Selections (257-258).