Recent Patents on Drug Delivery & Formulation - Volume 11, Issue 2, 2017

Background: This review is a continuation of preceding papers on invasive methods applied for diagnostics or drug delivery with questionable clinical indications and/or research purposes. It aims to serve as a reminder that the risk-to-benefit ratio should be kept as low as possible. Methods: Review of literature and Russian patents; author’s observations since 1983. Results: The use of bronchoscopy as a diagnostic and drug delivery method in asthma, bronchitis and tuberculosis is discussed in some detail. Bronchoscopy was applied in children and adults with asthma both during remissions and exacerbations, as well as pre-asthma defined as bronchitis with elements of bronchospasm and allergy. In the pediatric clinic of the Moscow medical academy, endoscopic methods have been applied in children and newborns for diagnostic, therapeutic and research purposes since the 1960s. Various bronchoscopic methods have been patented; several patents are presented here as examples. The concept of informed consent and assent applied to children and adolescents is also discussed. Conclusion: Significance of the procedural quality assurance in endoscopy is stressed, particularly, training methods not involving patients. It is also important to monitor endoscopic skills and objectively select capable trainees.

Background: In recent decades, the development of the environmentally responsive systems for drug delivery has been well regarded, with enormous potential in different applications. Methods: These environmentally sensitive, smart, intelligent formulations have the ability to alter their physical properties in response to small changes in physical or chemical conditions, such as temperature, glucose, pH, ultrasound, light, electric field and redox potential with a huge potential in drug delivery systems. The use of formulations containing smart materials enables to carry the drug to the target tissue, cells and release in a triggered way. Consequently, they have demonstrated several advantages like decreased dose frequency, ease of preparation and administration, prolonged release with reduced side effects, as well as, reduced costs when compared to conventional processes for industrial applications. In this sense, many patents have deposited, displaying different pharmaceutical devices using responsive systems. Results: There are more than twenty-five patents deposited about thermoresponsive systems. Furthermore, a few number of patents within glucose responsive, ultrasound responsive and light responsive deposited. There also are about eight patents that are pH-responsive, four as electric-field responsive. Most of them cover more than one type of stimuli. Conclusion: Therefore, in this review, since 1975 to 2016, we have categorized, reviewed and discussed the patents, applications, pharmaceutical dosage forms, the importance and perspectives of this environmentally responsive approach as potentially useful therapeutic modality.

Background: The aim of this review is to provide an insight to the underlying biomedical applications of magnetic nanoparticles (MNPs). Methods: The most specific characteristic of MNPs is their response to an applied magnetic force, and this property of MNPs has been utilized in applications such as diagnosis of diseases, drug delivery and drug targeting. Currently, MNPs have attracted great attention because of their potential as contrast agents for magnetic resonance imaging (MRI) and heat mediators for cancer therapy (hyperthermia). Results: Furthermore, the MNPs are also being used to achieve targeted delivery of biological molecules. Nowadays cancer is one of the biggest challenges and our goal is not only to improve the therapeutic outcome, but also to improve the methods of treatment along with the minimum adverse effect. Some suitable conclusions have been quoted on the precise synthesis approaches by focusing the mechanism of MNPs and new modification made on the production of these nanoparticles. Conclusion: In this review diverse biomedical application of MNPs were also addressed and patents related remarks also made from the literature.

Background: Hydrogen sulfide (H2S) is a colorless gas with a characteristic smell of rotten eggs. Once only thought of as a toxic gas, evidence now shows that H2S plays major roles in pathological and physiological activities. These roles are being utilized to treat diseases and disorders ranging from hypertension, inflammation, edema, cardiovascular issues, chronic pain, cancer, and many more. Challenges facing the use of H2S currently involve achieving the optimum therapeutic concentrations, synthesizing chemically and physiologically stable donors, and developing clinically appropriate delivery systems. Methods: We did an extensive literature search on therapeutic potentials and related issues of H2S which were presented in a systematic flow pattern in introduction. Patents accepted/filed on various aspects of hydrogen sulfide were searched using the United States Patent and Trademark Office database at http://patft.uspto.gov/ and google patents at https://patents.google.com/. The important search terms combined with H2S were therapeutic effect, pharmacological action, biochemistry, measurement, and delivery. We also incorporated our own experiences and publications while discussing the delivery approaches and associated challenges. Results: In the process, researchers have discovered novel techniques in preparing the noxious gas by discovering and synthesizing H2S donors and developing controlled and predictable delivery systems. Donors utilized thus far include derivatives of anti-inflammatory drugs like H2S -aspirin, Allium sativum extracts, inorganic salts, phosphorodithioate derivatives, and thioaminoacid derivatives. Use of controlled delivery systems for H2S is critical to maintain its physiological stability, optimum therapeutic window, increase patient compliance, and make it easier to manufacture and administer. Numerous patents overcoming the challenges of using H2S therapeutically with various donors and delivery mechanisms have been reviewed. Conclusion: The scientific knowledge gained from the last decade researches has moved H2S from a foul smelling pungent gas to the status of a gasotransmitter with many potential therapeutic applications. However, developing a suitable donor and a delivery system using that donor for providing precise and sustained release of H2S for an extended period, is critically needed for any further development towards its translation into clinical practices.

Background: Naratriptan is second-generation triptan class of antimigraine drug which selectively bind with 5-HT(1B/1D) receptor. It is widely used to treat the migraine attack due to its better tolerability and lower recurrence rate as compared to other triptans. Despite of the applicability, Naratriptan also have several drawback like slow onset of action and fist pass metabolism which reduce its efficacy. In order to increase the efficacy of naratriptan fast dissolving film is prepared. Method: Fast dissolving film of Naratriptan hydrochloride was prepared by solvent casting method Based on the patent survey (US 7648712 B2, WO 2012053006 A2, US 20090047330 A1, EP 2821066 A4, WO 2008108940 A1, WO 2010151020 A3) excipients were screened to find out suitable combination of polymer and plasticizer and Hydroxypropylmethyl Cellulose (HPMC E6) and glycerol were selected as film forming polymer and plasticizer respectively. To study the effect of independent variables on dependent variables 32 full factorial design was applied using Concentration of HPMC E6 and Concentration of Glycerol as independent variables and disintegration time, folding endurance, tensile strength and cumulative % drug release at 2 min as dependent or response variables. A statistical model incorporating interactive and polynomial terms was utilized to evaluate the responses. Result & Conclusion: From the results of statistical evaluation batch F3 was selected as the optimized batch which exhibited shorter disintegration time (22sec) with satisfactory mechanical properties (tensile strength 652.17 gm/mm2). Dissolution of drug from F3 formulation was rapid with around 91% drug release in 120sec. Optimized batch was further evaluated for in vitro permeation study using Franz diffusion cell.

Objective: The fractionated coconut oil based Solid Lipid Nanoparticles (SLNs) of Acyclovir (ACV) were fabricated in two batches by using Glyceryl mono stearate (GMS) and Lipoid S75 (Fat free soybean phospholipids with 70% phosphatidylcholine-Lipoid GmbH, Germany). The research was focused on developing ACV-SLN by using high pressure hot-homogenization technique. The ingredients were used in different concentrations and ratios to identify the best formulation design. Methods: The GMS with Fractionated coconut oil and Lipoid S75 with Fractionated coconut oil were used in various concentrations in formulation design to assess the impact on the fabrication and evaluation of SLNs. The SLNs were subjected to various characterization techniques such as XRD (X-Ray Diffraction), FTIR (Fourier transform infrared study), master sizer analysis and zeta potential. The mean particle size was determined by master sizer and zeta sizer. Transmission Electron Microscopy (TEM) was used as a tool to analyze the morphology and other features. The zeta potential and drug Entrapment Efficiency (EE%) were also determined. The drug release time profile was studied in vitro study with the utilization of dialysis membrane technique as well as by wistar rat skin. The most recent patents related to the current research topic were also discussed. Results: The Zeta potential of the best formulation from GMS batch GNE5 was found to be -2.62mV as the preparation was very viscous with low zeta potential. The better results of Lipoid S75 batch LS4 were found to be 23.23mV which was within the recommended range. The formulations prepared with Lipoid S75, LS4 showed narrow distribution size of 53.46nm and the uniformity was found to be 14.1. The formulation LS4 demonstrated the lowest distribution with of 6.8, 14.5, 139.1nm respectively amongst all the formulations. Conclusion: SLN dispersions exhibited the average size in nano range. SLNs with small particle size found to have predetermined encapsulation efficiency and relatively high loading capacity and predetermined in vitro drugrelease profile. The lipoid S and Pluronic F68 nanoparticles are found to be superior to Conventional GMSand tween 80 nanoparticles in terms of particles size, stability and zetapotential.

Background: Low aqueous solubility is a major problem faced with new drug molecules. The purpose of this research was to provide a fast dissolving oral dosage form of Gliclazide (GLZ) using the concept of mixed hydrotropy. The recent patents on Adenosine (US20140107059A1), Growth hormone releasing factor peptide (EP0984788A1) and Paclitaxel (WO2002030466A2) helped in selecting the hydrotropes. Methods: Solubility of GLZ was determined individually in sodium salicylate, nicotinamide, lactose, sodium acetate, urea, trisodium citrate and sodium benzoate. Highest solubility was obtained in 40% sodium benzoate solution. In order to decrease the individual hydrotrope amount, mixed hydrotropic agents were used. Results: Highest solubility was obtained in 25:15 ratio of sodium salicylate and sodium benzoate. This optimized combination was utilized in the preparation of solid dispersions which were evaluated for Xray diffractometry, Differential Scanning Calorimetry (DSC) and Fourier-transform infrared to show no drug-hydrotropes interaction. This solid dispersion was compressed to form fast dissolving tablets. Dissolution studies of prepared tablets were done using USP Type II apparatus. Conclusion: The batch G3 tablets showed 86% cumulative drug release within 14min with in vitro dispersion time of 33sec. It was concluded that the enhancement in solubility of GLZ is a clear indication of the potential of mixed hydrotropy which is a novel, safe and cost-effective technique to be employed for other poorly water-soluble drugs having low bioavailability.