Recent Patents on Drug Delivery and Formulation最新文献

Introduction: Although considerable efforts have been made to develop effective therapeutic agents for Alzheimer's Disease (AD), neither a consensus concerning the pathogenesis of the disease nor a successful therapy for its treatment is yet available. The natural product chemistry brings tremendous diversity and abundant resource for medical needs.

Objectives: The present review summarizes recent patents on natural extracts and derived drugs as agents for the prevention and treatment of AD. It also sums up the suggested mechanisms of action of the formulated natural remedies.

Conclusion: It is now becoming well accepted that multiple factors contribute to the progression of AD. The pathogenesis of the disease involves amyloid-β cascade, tau hyperphosphorylation, oxidative stress, inflammation, mitochondrial dysfunction, protein misfolding, gene mutation, etc. It has been suggested that the multifactorial nature of AD pathogenesis requires the design of medicines with a wide spectrum of activity. Medicinal herbs are known to consist of multiple compounds and may implicate multiple mechanisms, thus being advantageous over the simple single-target drugs in the treatment of complex diseases. Indeed, natural products attract increased attention. In the last decades, they have become a major focus in the quest for AD remedies and may represent a real promise for curing the disease.

Background: Nabumetone is biopharmaceutics classification system (BCS) class II drug, widely used in the treatment of osteoarthritis and rheumatoid arthritis. The most frequently reported adverse reactions for the drug involve disturbance in gastrointestinal tract, diarrhea, dyspepsia and abdominal pain. Microemulgel has advantages of microemulsion for improving solubility for hydrophobic drug. Patent literature had shown that the work for drug has been carried on spray chilling, enteric coated tablet, and topical formulation which gave an idea for present research work for the development of transdermal delivery.

Objective: The objective of the present research work was to optimize transdermal microemulgel delivery for Nabumetone for the treatment of arthritis.

Methods: Oil, surfactant and co-surfactant were selected based on solubility study of the drug. Gelling agents used were Carbopol 934 and HPMC K100M. Optimization was carried out using 32 factorial design. Characterization and evaluation were carried out for microemulsion and microemulsion based gel.

Results: Field emission-scanning electron microscopy (FE-SEM) study of the microemulsion revealed globules of 50-200 nm size. Zeta potential -9.50 mV indicated good stability of microemulsion. Globule size measured by dynamic light scattering (zetasizer) was 160nm. Design expert gave optimized batch as F7 which contain 0.2% w/w drug, 4.3% w/w liquid paraffin, 0.71% w/w tween 80, 0.35% w/w propylene glycol, 0.124% w/w Carbopol 934, 0.187% w/w HPMC K100M and 11.68% w/w water. In-vitro diffusion study for F7 batch showed 99.16±2.10 % drug release through egg membrane and 99.15±2.73% drug release in ex-vivo study.

Conclusion: Nabumetone microemulgel exhibiting good in-vitro and ex-vivo controlled drug release was optimized.

Background: While protein therapeutics are invaluable in managing numerous diseases, many require frequent injections to maintain therapeutically effective concentrations, due to their short half-life in circulation. PolyXen™, a platform and patented technology employing biodegradable, non-immunogenic and hydrophilic Polysialic Acids (PSA) for drug delivery, is being utilized to overcome such limitations, thereby potentially enabling the clinical utility of a broad range of protein therapeutics. Here, we report the recent progress on two development candidates, polysialylated deoxyribonuclease I (PSA-DNase) and polysialylated erythropoietin (PSA-EPO).

Methods and results: Chemical polysialylation of DNase I (DNase) using PSA with different chain length at various conjugation sites led to improved stability against proteases and thermal stress, and slightly reduced enzymatic activity. Polysialylation of EPO resulted in retention of protein structure and PSA-EPO remained biologically active. PSA-EPO had a significantly prolonged circulating half-life (e.g. t1/2 of PSA-EPO = ~400 h in patients after subcutaneous administration, aimed for once monthly administration, vs. t1/2 of EPO = ~22 h; administered twice or thrice weekly), and retained in vivo efficacy.

Conclusion: This approach has been clinically validated in phase I (in healthy volunteers) and II studies of PSA-EPO [for managing anemia in patients with chronic kidney disease (CKD)].

Aims and background: The fundamental objective of current study was to encapsulate Aripiprazole (ARP) within Pluronic F127 micelles to improve its aqueous solubility. The recent patents on Aripiprazole (JP2013136621) and micelles (WO2016004369A1) facilitated selection of drug and polymer.

Materials and methods: The drug-laden micelles were fabricated using thin-film hydration technique. Optimization of the micellar formulation was done by using response surface method (RSM). The Pluronic F127 concentration of 150 mg and 75 rpm rotational speed of rotary evaporator were found to be optimized conditions for formulating micelles.

Results: The prepared batches were further characterized for PDI (polydispersity index), zeta potential, % DLC (% Drug loading content), % EE (% Entrapment Efficiency) and % drug release study; results of these parameters were found to be 0.228, -4.04 mV and 76.50 % and 18.56 % respectively. It was observed from the In vitro release study that 97.37 ± 1.81 % drug had released from micelles after 20h which were found about thrice as compared to that of pure drug. The optimized ARP micellar formulation was characterized using DSC (Differential Scanning Colorimetry), FT-IR (Fourier Transformed Infrared Spectroscopy), P-XRD (Powdered X-ray Diffraction Study) and TEM (Transmission Electronic Microscopy) studies. ARP-loaded micelles displayed a hydrodynamic diameter of 170.3 nm and a sphere-shaped morphology as determined by dynamic light scattering as well as TEM study.

Conclusion: It is concluded that the prepared polymeric micellar system has an excellent potential to be used as a delivery carrier for Aripiprazole with increased solubility.

Objective: The aim of the present investigation entails the development of solid SMEDDS for improving the oral bioavailability of canagliflozin using porous carriers. The previous patent (WO2017046730A1) was based on enhanced solubility of canagliflozin through co-crystal formation.

Methods: Preconcentrates were prepared by employing Lauroglycol (80 mg), Tween 80 (300 mg) and Transcutol P (120 mg) and successfully adsorbed onto various hydrophilic and hydrophobic carriers. The prepared solid SMEDDS were characterized for various parameters to determine the optimized formulation. In vitro, ex vivo and in vivo studies were carried out to determine drug release kinetics, permeation and absorption rate, respectively. Stability of the formulation was investigated at 45°C/75% RH.

Results: The solid preconcentrates prepared with hydrophobic carriers exhibited desired attributes in a uniform range. Neusilin adsorbed solid SMEDDS (S(N)SMEDDS) portrayed enhanced amorphization in XRD and DSC studies and found to be physically compatible in FTIR studies. SEM revealed colloidal particles having spherical morphology with negligible aggregation. Ex vivo permeation rate of the drug across excised intestinal segments (duodenum, jejunum, ileum and colon) was observed to be 3.72, 5.85, 4.51 and 3.0-fold, respectively, as compared to pure drug. TEM of reconstituted SMEDDS indicated nano-sized globules with negligible coalescence. Enhanced in vitro dissolution rate of optimized solid SMEDDS manifested in bioavailability enhancement of 167.54% and 188.98%, as compared to pure drug and marketed product. These studies further substantiate the lymphatic uptake of SMEDDS through chylomicron flow blocking approach. Establishment of Level A IVIVC showed a uniform correlation between the in vitro dissolution efficiency and in vivo pharmacokinetic parameters.

Conclusion: The present investigation reveals the immense potential of solid SMEDDS in augmenting the oral bioavailability profile of poorly water-soluble drug canagliflozin.

Aims and background: The design and development of an effective medicine are, however, often faced with a number of challenges. One of them is the close relationship of drug's bioavailability with solubility, dissolution rate and permeability. The use of curcumin's (CUR) therapeutic potential is limited by its poor water solubility and low chemical stability. The purpose was to evaluate the effect of polymer and solid dispersion (SD) preparation techniques to enhance the aqueous solubility, dissolution rate and stability of the CUR. The recent patents on curcumin SD were reported as (i) curcumin with polyvinylpyrrolidone (CN20071 32500 20071214, WO2006022012 and CN20151414227 20150715), (ii) curcumin-zinc/polyvinylpyrrolidone (CN20151414227 20150715), (iii) curcumin-poloxamer 188 (CN2008171177 20080605), (iv) curcumin SD prepared by melting method (CN20161626746-20160801).

Materials and methods: SD obtained by co-preciptation or microwave fusion and the physical mixture of CUR with Poloxamer-407 (P-407), Hydroxypropylmetylcellulose-K4M (HPMC K4M) and Polyvinylpyrrolidone-K30 (PVP-K30) were prepared at the ratios of 1:2; 1:1 and 2:1. The samples were evaluated by solubility, stability, dissolution rate and characterized by SEM, PXRD, DSC and FTIR.

Results: The solubility, stability (pH 7.0) and dissolution rate were significantly greater for SD (CUR:P-407 1:2). The PXRD,SEM and DSC indicated a change in the crystalline state of CUR. The enhancement of solubility was dependent on a combination of factors including the weight ratio, preparation techniques and carrier properties. The drug release data fitted well with the Weibull equation, indicating that the drug release was controlled by diffusion, polymer relaxation and erosion occurring simultaneously.

Conclusion: Thus, these SDs, specifically CUR:P-407 1:2 w/w, can overcome the barriers of poor bioavailability to reap many beneficial properties.

Background: Nanopharmaceutical is the field that arises gradually but many challenges are also still there. This review aims to identify these challenges and give the focus on their rectification.

Methods: In this paper, we memorize the safety issues, patented manufacturing procedure, applications and regulatory aspects of the nanopharmaceuticals by using the peer-reviewed research literatures. All the screened literatures described the quality content of nanopharmaceuticals with relevancy to biomedical and pharmaceutical field.

Results: Nanopharmaceuticals have great potential to resolve the different issues such as; site specific drug delivery however, many challenges are also arising in their commercialization. In the recent years, some nanopharmaceuticals have the desired quality and safety for the public, have been approved by the regulatory agencies but this field is still a thrust area that demands a lot of attention.

Conclusion: The present review article confirms the importance of nanopharmaceuticals and impart the knowledge for making the significant approaches and strategies to overcome the manufacturing, safety, legal and regulatory issues related to nanopharmaceuticals.

Background: Nanotechnology-based drug delivery approach has emerged as a promising field, where different kinds of formulations are developed for therapeutic applications. Inflowing of nanomedicine developed through various biomaterials appears to be a game changer in the domain of pharmaceutical and biotechnological industries. Nanomedicines propose to overcome the major constraints of conventional medicine of low solubility and stability, non-adequate pharmacokinetic profiles and side effects.

Objectives: Mesoporous Silica Nanoparticles (MSNs) have garnered significant attention in biomedical applications for its multifunctionality. The porous structure of MSNs provides the opportunity for heavy drug loading, controlled release and ligand functionality. From last decades, a lot of interest has been generated owing to the better drug delivery attributes of MSNs to introduce unique biological effects for its suitable therapeutic application.

Methods: The review article gives an insight into the current advancement of usage of MSNs in drug delivery for cancer, non-cancer and biosensors based biomedical applications along with technology that is protected by patents.

Conclusion: The future success of MSNs is widened because of their valuable characteristic that easily combines with various functionalities which would display enormous potential translational possibilities.

Background: Nowadays, Oral Film Technology (OFT) has gained much attention among all the oral drug delivery systems. Fast dissolving film, fast disintegrating film, and orodispersible film are some synonymous words for this dosage form. Without a need of liquid for administration, this dosage form dissolves in the mouth. Typically, fast dissolving film dissolves from 1 to 30 seconds.

Objective: At the root of its originality, many researchers patented their work on the aspect of orodispersible films using different drugs, polymers, excipients and employing various methods of preparation. The review focuses on details related to orodispersible films and their patents from 1979-2017, collected from various sources like USPTO, Google patent, Espacenet, Intellectual Property India.

Results: For the ease of discussion, collected patents are segregated on the basis of drugs, polymers, and method of preparation. It was found that many researchers are shifting towards fast dissolving films for better patient compliance, extended efficacy, high bioavailability, fast dissolution, and disintegration. With the help of polymers blend suitable for the drug release and improved method of preparation various parameters like tensile strength, thickness, and pH etc. can be controlled.

Conclusion: It was observed that judicial selection of polymers and polymers blends and methods of preparation are key parameters in the formulation of orodispersible film.

Background: For the past few decades, there has been considerable research interest in drug delivery strategies using nanoparticulate systems as carriers for a wide range of active pharmaceutical ingredients.

Objective: It is known that nanoparticulate drug delivery systems comprise a wide variety of dosage forms including nanospheres, micelles, solid lipid nanoparticles, nanoliposomes, dendrimers, magnetic nanoparticles, and nanocapsules.

Methods: This review describes nanocapsule preparation techniques and their applications for the treatment of several diseases using patents and examples from the literature.

Results: Nanocapsules are vesicular systems consisting of an inner liquid core (aqueous/oily) surrounded by a polymeric wall that has immense potential as drug carriers because of the many advantages like improving poor aqueous solubility, stabilizing drugs by protecting the molecule from the environment, providing the desired pharmacokinetic profile, allowing controlled release, as well as facilitating oral administration.

Conclusion: The present study discusses and summarizes patents related to preparation methods of and recent studies from the last 10 years on nanocapsules as drug delivery systems.