Recent Patents on Drug Delivery and Formulation最新文献

Aim and background: The rationale of this study is that, treatment of asthmatic Guinea pig with combined administration of Montelukast sodium and Green Tea Extract (GTE) as a single capsule will mitigate the inflammatory injury in the airways and weaken the asthmatic response. Recent patents for the treatment of asthma researched a polyphenolic alternatives for antiasthmatic combination therapy, especially for those patients who remains unresponsive or poorly responsive for current asthma therapy (US7232585B2). Synergistic activity of green tea polyphenols and therapeutic, prophylatic agents are also reported in some recent patents (US20120172423A1, US20150320696A1). The present work is therefore aimed, to study the effect of Montelukast Sodium capsules coformulated with GTE on oxidative stress markers including Malondialdehyde (MDA), Glutathione (GSH) in different organs and Oxygen Radical Absorbance Capacity (ORAC) assay in plasma.

Materials and methods: Guinea pigs were placed in histamine chamber and exposed to an aerosol challenge of 0.2% w/v histamine dihydrochloride in distilled water using pressurized air driven nebulizer at a pressure of 0.05 MPa-0.106 MPa for one week. After that, they were divided in to four groups of three each; control, asthmatic control, asthmatic treated with marketed preparation and asthmatic received developed capsules. After oral administration of formulations for three days, pigs were scarificed and oxidative stress markers level including cytoarchitectural manifestation in tissues was studied.

Results: In comparison with the healthy control group, MDA level of the asthmatic animal liver and lung was found to be elevated as 0.059 ± 0.031(p < 0.002) and 0.802 ± 0.310 (p < 0.005) respectively, whereas GSH level was declined as 13.223 ± 1.485 (p < 0.0001) in liver and 3.037 ± 0.282 (p < 0.0004) in lung tissues. TAC of asthmatic animal plasma was low as 2.132 ± 0.986 mM Trolox Eq/L (p < 0.009). The level of these biomarkers reverts back towards normal after treatment with marketed and developed formulation, although treatment with developed formulation was more efficacious since it was coformulated with GTE, which acts as an adjuvant for the management of inflammatory disease like asthma.

Conclusion: It is contemplated that, use of GTE as an adjuvant to anti leukotriene drug played a significant role in asthma management by reducing oxidant injury. Since, studies in animals do not directly translate to human biology, further multi-control studies with better sampled patient population and more number of patients are needed.

Skeletal muscle is a highly-specialized tissue that is capable of contractile function and able to withstand and adapt to daily mechanical and physiological stress. Musculoskeletal disorders, including muscular dystrophies, result in chronic pain and disability, reduced quality of life, burden on family, and increased healthcare costs. Although several mechanisms have been identified for muscle injury and regeneration, mechanisms of these diseases are poorly understood, and targeted and effective pharmacologic treatment(s) are not available. More research is needed in this area in order to develop effective treatment regimens. The purpose of this review is to discuss known mechanisms of muscle injury and repair, and highlight some recent patents and research developments for treatment of skeletal muscle disorders.

Background: From the past few decades, remarkable awareness has laid on the use of herbal medicines in pharmaceutical research. Thymoquinone (TQ), the main chemical constituent of Nigella Sativa (NS) plant, has been extensively explored, and revealed an array of therapeutic benefits, in different in vitro, and in vivo conditions. This review provides brief outline of the diverse therapeutics actions of TQ, and NS, viz. anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, gastroprotective, hepato-protective, anti-microbial and anti-histaminic. Besides, a special emphasis has given on the use of colloidal drug delivery systems exploited hitherto, for the effective delivery of TQ and NS.

Objective: The main objective of the review was to include an intensive patent literature, available on TQ and NS, for its usefulness in different therapeutic conditions.

Methods: We embarked an organized search of bibliographic databases for peer-reviewed research literature and patent databases. The characteristics of screened papers were described, and a rational qualitative content analysis approach was applied to analyze the interventions and findings of included studies using a theoretical framework.

Results: In the past, various studies have carried out which undoubtedly vouch for the multifarious therapeutic roles of TQ in an array of different diseases. More than 670 research papers and around 50 review articles are available on TQ and NS in PubMed database until now, suggesting its high significance. Around 12 review articles published only on the anticancer potential, while the others on its anti- inflammatory and anti-oxidant potential. Around 120 papers included in the review revealed the therapeutic benefits of TQ. In addition to this, an intensive patent literature is also available on TQ and NS, for its usefulness in different therapeutic conditions.

Conclusion: The findings of this review confirm the effectiveness of TQ in various pathologies viz. inflammation, cancer, diabetes, gastric, hepatic, microbial and allergies. However, the complete clinical benefit of TQ has not yet been realized, owing to its poor biopharmaceutical properties. Nevertheless, colloidal drug delivery carrier systems, could be impending in bringing forth this potential molecule to reality.

Background: Herbal drugs are gaining exponential scientific recognition due to their distinct advantages. In the last 2-3 decades, a gradual increase in worldwide patents on herbal nanoformulations has been noted to address the solubility and bioavailability issues of phytoceuticals. Struvite or ammonium magnesium phosphate hexahydrate (NH4MgPO4.6H2O) is among the important urinary infection stones causing painful urological ailment. These smaller stones may bind together to form bigger staghorn calculus. Urinary tract infections caused by some gram positive and gram negative bacteria further enhance the chance of formation of such stones. Oxalis corniculata Linn. is an edible plant, traditionally used in the treatment of bacterial infections and kidney stones. However, there is no scientific evidence to relate the use of O. corniculata against struvite kidney stones. Hence, the antibacterial and struvite stones inhibition activity of the aqueous extract of Oxalis corniculata Linn. leaves and its biofabricated silver nanoparticles (AgNPs) was studied.

Methods: The aqueous extract of O. corniculata was prepared by Soxhlet extraction. AgNPs were synthesized using green technique and were characterized using UV and IR spectroscopy, XRD, TEM, DLS and zeta potential studies. Antibacterial activity of the aqueous extract and the silver nanoparticles was tested against E. coli (gram negative) and S. aureus (gram positive) species. Struvite stones were grown in a gel medium by in vitro single diffusion gel growth technique and its inhibition study was carried out using the extract and its biofabricated nanoparticles.

Results: The aqueous extract and its biofabricated AgNPs exhibited potent antibacterial activity against both gram positive and gram negative strains of bacteria. The aqueous extract also effectively repressed the growth of struvite stones and led to the dissolution of stones, but the inhibitory effect was further enhanced by its biofabricated AgNPs.

Conclusion: The present work confirms the inhibitory activity of the aqueous extract of edible O. corniculata and its biofabricated silver nanoparticles against urinary tract infection (UTI) causing bacteria and urolithiasis. Therefore, the consumption of O. corniculata in our daily diet may reduce the risk of UTI and urolithiasis.

Purpose: The purpose of the study was formulation development, optimization and evaluation of a Self-Emulsifying Drug Delivery System (SEDDS) of Simvastatin (SIM) for improvement in dissolution and bioavailability of SIM. Solubility enhancement of Biopharmaceutical Classification System (BCS) Class-II drugs is a burning topic and attracting various publications and patents regarding different strategies employed for improvement of dissolution viz., USOO5340591A (Solid dispersion), US005472954A, US005646131A (complexation), USOO5858410A (Nanosuspensions), USOO5874029A (micronization) US2008.00095O2A1 (Solid composites), US2008O146640A1 (Prodrug) US 2009001 1009 A1 (nanocapsules), etc. Methods: SEDDS was prepared on the basis of solubility studies employing Capmul MCM EP as lipid and Cremophor ELP as surfactant. Box-Behnken design was implemented for optimization by using lipid concentration, surfactant concentration and mixing time as dependent variables and their impact was observed on particle size, poly dispersity index (PDI) and drug released in 15min. Optimized formulation was evaluated for particle size, PDI, zeta potential, emulsification time, transmittance, invitro drug release and in situ Single-Pass Intestinal Perfusion (SPIP) studies.

Results: For optimized formulation, OF1 value of particle size, PDI, zeta potential, emulsification time, transmittance and percent in-vitro release were 162±14.32nm, 0.19±0.01, -22.3 ±1.1mV, 93±3.11 sec, 99.45±4.35 % and 99.43± 5.6 % in 30 min respectively. In-situ SPIP studies were performed on Wistar rats and the value of predicted fraction absorbed for humans was found to be 0.98.

Conclusion: SIM SEDDS was successfully developed and evaluated for in-vitro & in-vivo parameters. All the evaluated parameters were in tolerable limits. In vitro release studies from optimized formulation, OF1, exhibited maximum drug release when compared to SIM API and marketed preparation. Moreover, the predicted value of fraction absorbed (Fa) in humans by in-situ SPIP method was also in agreement with in-vitro dissolution studies thus, confirming SEDDS as a suitable drug delivery system for solubility enhancement of SIM.

Background: Cervical cancer being the cancer of cervix is caused by an aberrant cell growth that acquires an ability to spread/ invade to other body parts. It has also been reported to be the second most common cause of death and cancer among women. Based on the severity of the disease, treatment aspects need to be explored more in order to overcome the limitations acquired by the conventional treatment. Recently, nanocarriers based drug delivery systems including liposomes, nanofibres, metallic NPs, polymeric NPs, dendrimers, polymeric micelles, antibody-drug conjugates, etc. have been explored to target and treat cervical cancer.

Objective: This review highlights numerous recent research and patent reports as well on nanocarriers based systems.

Methods: Patents viz US, EP and WIPO have been retrieved using sites www.uspto.gov/patft and www.freepatentsonline.com to collect literature on nanocarriers.

Results: Various research reports and patents revealed nanocarriers to be effective in treating cervical cancer and these carriers are observed to be safer than the conventional treatment.

Conclusion: Nanocarriers result in transforming drug distribution that can overpower drug resistance. Further, nanocarriers based drug delivery systems can particularly target drugs to cellular, subcellular and tissue sites. By enhancing the drug's bioavailability at the desired site, these systems result in therapeutic benefits like enhanced safety and efficacy. Also, in combination with other treatment approaches like radiation, photothermal and gene therapy, nanocarriers are reported to be quite effective and can define novel strategies to combat cervical cancer.

Aims and background: The number of pathogenic microorganisms has been increasing over the years, and so as resistance of these microorganisms are developing against various antibiotics. Antimicrobial photodynamic therapy (aPDT), also called photodynamic inactivation, is emerging as a promising alternative to treatments based on conventional antibiotics. Recent patents on structured silver mesoporous silica nanoparticles having antimicrobial activity (WO2010/071831 A2), photosensitiser modified core-shell structure nanocomposites (CN 103536935(A)), and Chitosan-coated magnetic mesoporous silica nanoparticles (MSN) (CN 104785214(A)) helped in selecting method of synthesis of MSN and photosensitizers.

Materials and methods: MSN were synthesised by Sol-Gel method and amino functionalised (APTES). Methylene blue (MB) and ortho-toluidine blue (O-TB) were used as photosensitisers. Different batches were synthesised. The final product was characterised by using FTIR, BET, SEM, time resolved fluorescence. The photosensitiser loaded MSN were illuminated by LED based lamp emitting red light at 620± 20nm for different time lengths viz 15 min and 30 mins. Fluorescence studies and antimicrobial assays were carried out as per 72 well plate method I.P, 2014 using, gram negative E. coli (ATCC no. 8739), S. aureus (ATCC no. 7447) and gram positive P. aeruginosa (ATCC no. 9027) pathogenic microorganisms.

Results: MB and O-TB were successfully adsorbed on APTES functionalised MSN. Different exposure time length of the photosensitisers to red light showed different zone of inhibition. MB and O-TB loaded MSN showed significant increase in zone of inhibition after irradiation as compared to MB and O-TB loaded on MSN without exposure to light.

Conclusion: MB and O-TB adsorbed on APTES functionalized mesoporous silica nanoparticles were capable of efficiently inactivating E. coli, P. aeruginosa, S. aureus bacteria upon exposure to red light (620± 20nm wavelength) at a much lower concentration. Mesoporous silica nanoparticles played an important role in aPDT due to their high surface area and porous structure. Also, APTES functionalization resulted in the pore expansion of MSN, thereby increasing the loading capacity of the photosensitizer on MSN. From the results obtained it can be concluded that O-TB loaded MSN showed higher activity against gram negative and positive microorganisms microorganism as compared to that of MB.

Purpose: The solubility of drug is affected by various excipients present in formulation. In case of tablet formulation, the role of binders is very important for solubility of dosage form as well as drug. In this study, an attempt was made to improve the solubility and dissolution rate of a drug by the use of natural excipients. In this study, pear was selected for the extraction and isolation of starch. Then the extracted starch was used as a binder in different concentrations, in famotidine tablets and evaluates them. There are some recent patents on modified starch (WO2011002730A1), directly compressed starch (US6455069B1), pre-compacted starches (US4072535A), which helped in following the study.

Methods: The starch was isolated from natural source. Then, the tablets were formulated by wet granulation method by using 2% w/v, 4% w/v, 6% w/v and 8% w/v of pear starch as binding agent. Then formulated famotidine tablets were further evaluated for various parameters i.e. weight variation, hardness, thickness, friability, disintegration time and in-vitro drug release.

Results: The hardness and disintegration time of the tablets was found to be increased with increase in starch concentration. Tablets with the highest binder concentration showed maximum hardness (6.5 kg) and disintegration time (10min) and minimum friability (0.48%). After one hour, tablets with 4% w/v starch showed maximum drug release (80.69%).

Conclusion: The pear fruit used for the isolation of starch was a natural and a newer source. The obtained starch was safe, natural, economic and easily isolated in laboratory. The results from various evaluations show that pear starch has significant binding characteristics. Hence it can be used as tablet binder in pharmaceutical formulations in future in place of other costly and synthetic starch.

Aims and background: The objective of the study was to improve the bioavailability of poorly soluble repaglinide (RPG) by preparing nanosuspension with poloxamer 188 using high pressure homogenization (HPH). The recent patents on nanocrystals (US20150337006A1) facilitated selection of drug and polymer.

Methods: Suspensions containing dissimilar sized particles were prepared by ultrasonication and HPH. The prepared aqueous suspensions were lyophilized and then characterized. Further, the dried aqueous suspensions were evaluated for drug content, solubility, in vitro dissolution, oral bioavailability study and stability study.

Results: RPG nanoparticles size, polydispersity index (PDI) and zeta potential were found to be 280.8 ± 15 nm, 0.279 ± 0.04 and - 25.81 ± 1.6mV, respectively. DSC and XRD results showed that RPG particles in aqueous suspensions were present in a crystalline state; however, RPG nanoparticles exhibited decreased lattice energy due to smaller particle size. Nanoparticles prepared by HPH exhibited significant improvements in solubility and dissolution rate. Oral bioavailability was found to be enhanced by 1.93 fold in comparison with that of plain RPG. The nanosuspension was found to be stable when stored at 5°C ± 3°C.

Conclusion: The outcomes of the study revealed significant enhancement in dissolution rate and oral bioavailability of RPG due to size reduction to nano range by HPH.

Background: Drugs having absorption window in the stomach or upper small intestine have restricted bioavailability with conventional dosage forms. The gastric residence time of these dosage forms is usually short and they do not show drug release for prolonged period of time.

Objective: To avoid these problems and to enhance the bioavailability and gastric retention time of these drugs, controlled drug delivery systems with prolonged gastric retention time are currently being developed.

Methods: This review highlights the various pharmaceutical approaches for gastroretention such as floating drug delivery systems, mucoadhesive systems, high-density systems, expandable and swelling systems, super porous hydrogels systems, magnetic systems, ion exchange resin system and recent patents filed or granted for these approaches.

Results: Recently, some patents are also reported where a combination of various approaches is being employed to achieve very effective gastroretention. The various patent search sites were used to collect and analyze the information on gastroretentive drug delivery systems.

Conclusion: The present study provides valuable information, advantages, limitations and future outlook of various gastroretentive drug delivery systems.