Recent Patents on Drug Delivery & Formulation - Volume 11, Issue 3, 2017

Background: Neurodegenerative disorders are among the most common challenging diseases that affect the population with extreme medical and financial burdens. Widely seen neurodegeneration affects population of all ages, as it progresses with age, affecting a large proportion of elderly population including patients, caregivers, and immensely increasing the financial load of the country. These diseases have a very complex nature that frequently results from combined genetic, environmental and pathological factors. Various challenges are faced by the researchers working on the pathogenesis and the possible treatment of neurodegenerative disorder. Objective: The review has analysed for recent patent documents and treatment approaches for neurodegenerative disorders. This review does not relate to potential targets such as ( i.e. protein where modulation could be predicted to impact on pathophysiology), rather it mainly focuses on various available patented approaches for neurodegenerative disorders. Method: The study design is based on updating the international and national literatures and an exhaustive patent search, compiling various patented documents for the treatment of neurodegenerative disorders (EP2282779A1, US20110229555A1) to provide information in the state of technological innovation in terms of research and development. Results: In the present review, the authors described various neurodegenerative diseases, there treatment strategies and emphasized on various patented approaches for age-related neurodegenerative disorders such as novel therapeutic methods for treating Alzheimer's and associated disorders via modulated cell stress response EP2282779A1, through combined therapies that modulate angiogenesis US20120058992A1. Conclusion: The review will attract the interest of academics, researchers, students and pharmaceutical companies with regard to the recent on-going activities in neurodegenerative disorders.

Background: The quest to improve the therapeutic effectiveness of herbal drugs has driven the pharmaceutical research towards the development of herbal nanoparticles. Objective: Till date, various approaches have been adopted for the design of herbal nanoparticles. Methods: We carried out an organized search of bibliographic databases consisting of an ample number of published abstracts and research articles using a focused review questionaries and insertion/ omission criteria. The study was systematically structured to review various phytochemicals formulated as nanoparticles, understand its need and prospects. Indeed, research cited has revealed revival of some phytochemicals with therapeutic efficacy fronts. Results: Certain patents (US20170157005A1, US20160228362A1 and US20150050357A1) have evinced entrapment concerns of phytoceuticals into nanoparticles. Amongst various phytochemicals, Curcumin, Quercetin, Silymarin, Paclitaxel etc. seems predominant ones being successfully formulated as nanoparticles. The reason for the availability of their splendid formulations lies in the addresal of poor stability, poor water solubility and consequently poor bioavailability. Conclusion: If bioavailability constraint is overcome, diseases like cancer, Alzheimer's, diabetes, liver disorder etc. can be effectively targeted. By doing so, the largely affected society, will breathe the relief. The present article is an attempt to elaborate and conclude on how nanoparticles have been serving as a tool to enhance the effectiveness of phytochemicals, by solubilization, dissolution and consequent bioavailability enhancements, along with in vivo targeting. To further facilitate understanding, the review discusses disease/disorder and phytochemicals with focus on their nanoparticles.

Background: Furosemide is a potent diuretic agent used to treat pulmonary arterial hypertension. Variable dosage regimen and poor pharmacokinetic parameters have led to the development of transdermal drug delivery system. Objective: Patent on suitability of multi-lamellar structures for excellent transdermal delivery (US0367475A1) has encouraged us to formulate the solid lipid nanoparticles (SLNs) induced transdermal systems of furosemide to enhance the kinetic properties without incorporating any penetration enhancer and rate limiting polymers. Methods: SLNs were prepared by hot homogenization and ultra-sonication method; optimization was done based on entrapment efficiency and particle size. Optimized SLNs were incorporated in to transdermal patches by solvent casting method. In vitro and in vivo studies were carried out for characterization of transdermal patches. Results: SLNs of F9 (GMS: Span 60: Pluronic F 68 in 6:2.5:0.2) were optimized for incorporating in to transdermal system (entrapment efficiency 96.5±0.045%, particle size 69.6±1.48nm and in vitro release 94.38±1.02%). Transdermal patches were formulated using combinations of hydrophilic and hydrophobic polymers to study the diffusion kinetics. Formulation FS1 (HPMC 4 parts) was optimized for further studies (in vitro release 98.11±1.21% with flux of 58.726±0.023μg/cm2/h) and no significant difference from ex vivo permeation studies was observed. Drug release followed mixed order diffusion kinetics and super case –II transport mechanism. In vivo pharmacokinetic data of SLNs induced transdermal system suggested a 3.6 times increase in AUC and 5.4 times increase in MRT when compared with oral route. Conclusion: The SLNs induced transdermal patch was found to beneficial in enhancing kinetic properties both in vitro and in vivo.

Background: Prochlorperazine maleate (PCM) is a phenothiazine antipsychotic used in the treatment of nausea, vomiting and vertigo. It is BCS class II drug with only 12.5% bioavailability. Patents data on PCM had shown work on conjugation and matrix formulation which suggested idea for the present work design. Objective: The objective of this study was to enhance solubility of drug and to optimize gastro retentive floating capsule for controlled drug release at the targeted site for stipulated time. Method: The solubility of drug was determined in various vehicles like oils, surfactants and cosurfactants. Pseudo ternary phase diagrams were constructed to identify the efficient self emulsifying region. SMEDDS were tested for micro emulsifying properties. The resultant microemulsions were evaluated and were further selected for the floating drug delivery. Magnesium hydroxide was used as carrier to transform SMEDDS into Solid SMEDD (S-SMEDD). Non-effervescent floating capsule containing S-SMEDD were optimized using factorial design with independent variable HPMC K4M and ethyl cellulose. Results: SMEDD consists of PCM, isopropyl myristate, tween 80 and PEG 400 as a drug, oil, surfactant and co-surfactant (1:1 ratio). Optimized formulation F5 showed 10 hrs floating time and percent drug release 91.56±2.7% with controlled drug delivery in stomach. F5 followed Korsmeyer Peppas release kinetics where the drug followed Fickian diffusion transport mechanism due to swelling of polymers in controlled manner. Conclusion: It can be concluded that SMEDD enhanced the solubility of drug and floating capsule gave site specific drug release of PCM with the advantages of reduced dosing frequency and better compliance.

Background: Recent patents reveal that Soluplus® has proved to be a promising excipient that modulates dissolution characteristics of many active pharmaceutical ingredients (WO2016161995A1, WO2016169534A1 and WO2016165676A1). Objective: Current article investigates stable solid solution of furosemide with Soluplus® to enhance the dissolution properties of the drug. Method: Drug to carrier ratios to prepare solid dispersion were selected based on the phase solubility study. Solid dispersions of furosemide with Soluplus® were prepared by solvent evaporation and fusion methods. Physicochemical parameters were characterized using Fourier transform infra-red spectrophotometer, thermo- gravimetric analyzer, differential thermal analyzer, and scanning electron microscopy. Drug release from the formulations was compared using USP type II (paddle type) dissolution apparatus containing 900 mL of phosphate buffer (pH - 6.8) maintained at 37±0.5°C at a paddle rotation speed of 50rpm. Results: Fourier transform infra-red spectroscopy confirmed absence of any chemical interaction while thermo-gravimetry and differential thermal analysis showed evidences of formation of a solid solution of furosemide. No furosemide crystals were observed under scanning electron microscope in case of solid dispersion. Dissolution data indicated that furosemide dissolution was enhanced to a great extent and drug to carrier ratio of 1:10 was found to be most suitable. Conclusion: Solid dispersions prepared by fusion method exhibited faster drug release compared to those prepared by solvent evaporation.

Background: Poor oral absorption of budesonide limits the design of its solid oral dosage form. With this context, multiparticulate pulsatile system of budesonide for chronotherapy of nocturnal asthma was aimed in this study. Methods: Initially, solid dispersions of budesonide (BD) using sodium starch glycolate (SSG) and guar gum (GG) were developed and characterized. Uniform sized non-pareil seeds (~400 μm) were coated with solid dispersions to obtain immediate (BMP) and controlled release pellets by solution layering technique. Rationale of selection of BD in this research was based on recent patents such as diltiazem HCl (US5914134) and multipar-ticulate systems (US5017381). Pulsatile drug release pellets (BMPP) of BD were obtained by coating the controlled release pellets with Eudragit L100 and RS 100. Pellets were assessed by saturation sol-ubility, FTIR, DSC, micromeritic, SEM, drug content, drug release, pharmacokinetic and stability studies. Results: Solubility of BD was increased by 22 folds due to inter-particle distribution of BD and polymers in solid dispersions. No changes in characteristic functional groups of BD had indicated the compatibility of drug with polymers as noticed in FTIR and DSC. Fluidized bed processor enabled the production of spherical and uniformly distributed pellets with optimum angle of repose (12-19°) and friability (<1%). Solution layering technique employed in preparation of pellets had facilitated with moderately high BD content (91.5-99.6%) and 100% drug release at the end of 12hr. The pulsatile release pellets (BMPP) produced 6hr lag phase followed by 12hr controlled release. Promised pharmacokinetics was resulted as Cmax of 380ng/ml for BMP-2 and 162ng/ml for BMPP-5 and Tmax of 5 hr for BMP-2 and 12hr for BMPP-5. Increased pharmacokinetics was the direct results of increased solubility of BD due to application of solid dispersion and solution layering on pellets. Conclusions: Chronopharmacokinetics of BD were achieved with the help of Eudragit coatings on pellets. The BMP and BMPP formulations were found to be reasonably stable over a period of time. Thus, optimal chronopharmacokinetics of BD was achieved successfully by multiparticulate pulsatile technology.