In Vitro and In Vivo Performance of Novel Spray Dried Andrographolide Loaded Scleroglucan Based Formulation for Dry Powder Inhaler.

BACKGROUND: Current therapy for pulmonary arterial hypertension (PAH) is unable to prevent progression of disease due to continuous infusions and multiple oral administrations. This resulted in the need of novel treatment which would target directly structural vascular changes that weaken blood flow through pulmonary circulation. OBJECTIVE: The objective of present study was to develop spray dried (SD) formulation for dry powder inhaler (DPI) with enhanced aerosol performance and lung deposition by using novel bioactive, andrographolide (AGP) and carrier, scleroglucan (SCLG) with improved antihypertensive activity. The SDAGP formulation was evaluated for physicochemical properties and in vitro/in vivo lung deposition. Further, antihypertensive activity was studied by monocrotaline (MCT) induced rat model. RESULTS: The SDAGP exhibited mean median aerodynamic diameter (MMAD) and fine particle fraction (FPF) of 3.37 ± 0.47 µm and 60.24 ± 0.98%. The in vivo absorption profile of final formulation reflected increased lung deposition of AGP at the end of 24 h with no signs of inflammation and toxicity. Moreover, SDAGP formulation confirmed enhanced antihypertensive activity. CONCLUSION: The results proved use of AGP and SCLG as a novel bioactive and carrier with enhanced lung deposition and pulmonary antihypertensive activity.

Enhanced hepatoprotective activity of andrographolide complexed with a biomaterial.

CONTEXT: Humic acid (HA), a natural organic matter is recently being investigated for pharmaceutical purposes. Andrographolide (AGP), a potent hepatoprotective, possesses low aqueous solubility which results in a low bioavailability after oral administration, inappropriate tissue localization and consequently poor therapeutic application. OBJECTIVE: The present study investigates the complexation of AGP with HA to increase its solubility and hepatoprotective efficacy. MATERIALS AND METHODS: Complexes prepared by solvent evaporation in various weight ratios were characterized using differential scanning calorimetry, Fourier Transform InfraRed spectroscopy, X-ray diffraction, and scanning electron microscopy. RESULTS AND DISCUSSION: The complexed AGP demonstrated improved solubility, dissolution, and permeation across rat intestine. It also displayed better hepatoprotection against carbontetrachloride-induced liver toxicity than the free drug in rats. CONCLUSION: Complexation with HA is a valuable technique to improve solubility and bioavailability of pharmaceuticals.

Investigation of ethyl cellulose microsponge gel for topical delivery of eberconazole nitrate for fungal therapy.

BACKGROUND: The aim of the study was to investigate ethyl cellulose microsponges as topical carriers for the controlled release and cutaneous drug deposition of eberconazole nitrate (EB). MATERIALS & METHOD: EB microsponges were prepared using the quasiemulsion solvent diffusion method. The effect of formulation variables (drug:polymer ratio, internal phase volume and amount of emulsifier) and process variables (stirring time and stirring speed) on the physical characteristics of microsponges were investigated. The optimized microsponges were dispersed into a hydrogel and evaluated. RESULTS & DISCUSSION: Spherical and porous EB microsponge particles were obtained. The optimized microsponges possessed particle size, drug content and entrapment efficiency of 24.5 µm, 43.31% and 91.44%, respectively. Microsponge-loaded gels demonstrated controlled release, nonirritancy to rat skin and antifungal activity. An in vivo skin deposition study demonstrated fourfold higher retention in the stratum corneum layer as compared with commercial cream. CONCLUSION: Developed ethyl cellulose microsponges could be potential pharmaceutical topical carriers of EB in antifungal therapy.

Fisetin-loaded nanocochleates: formulation, characterisation, in vitro anticancer testing, bioavailability and biodistribution study.

BACKGROUND: The natural flavonoid fisetin has shown anticancer properties but its in vivo administration remains challenging due its poor aqueous solubility and extensive in vivo metabolism. This juncture demands an effective, controlled release and safe formulation of fisetin would be a significant advance for the treatment of cancer. OBJECTIVES: Nanocochleates are unique lipid-based supramolecular assemblies composed of a negatively charged phospholipid and a divalent cation. The aim was to develop and evaluate fisetin-loaded nanocochleates to improve its therapeutic efficacy. Using the trapping method, fisetin-loaded dimyristoylphosphatidylcholine liposomal vesicles were converted into nanocochleates by the action of Ca(2+) ions. These nanocochleates were further evaluated for physicochemical, in vitro anticancer and haemolysis, pharmacokinetics and tissue distribution study in mice. RESULTS: Stable rolled-up layers as well as elongated structure of nanocochleates possessing particle size and encapsulation efficiency (EE) of 275 + 4 nm and 84.31 ± 2.52%, respectively were obtained. Nanocochleates demonstrated safety and a sustained release of fisetin at physiological pH. A 1.3-fold improvement in vitro anticancer towards human breast cancer MCF-7 cells was observed. Pharmacokinetics studies in mice revealed that nanocochleates injected intraperitonially showed a 141-fold higher relative bioavailability. Moreover, a low tissue distribution was observed. CONCLUSION: Developed nanocochleates markedly improved anticancer efficacy, bioavailability and safety of fisetin. The nanocochleates technology would facilitate the administration of this flavonoid in the clinical setting. AREAS COVERED: In this research article, we focused on lipid-based supramolecular assembly 'nanocochleates' composed of negatively charged phospholipids and divalent cation as drug carrier for systemic delivery system and discussed their formulations, optimisation, characterization, in vitro and in vivo performance.

Development of plumbagin-loaded phospholipid-Tween® 80 mixed micelles: formulation, optimization, effect on breast cancer cells and human blood/serum compatibility testing.

BACKGROUND: Phospholipid and Tween(®) 80 mixed micelles were investigated as injectable nanocarriers for the natural anticancer compound, plumbagin (PBG), with the aim to improve anticancer efficiency. PBG-loaded mixed micelles were fabricated by self-assembly; composition being optimized using 3(2) factorial design. RESULTS & DISCUSSION: Optimized mixed micelles were spherical and 46 nm in size. Zeta potential, drug loading and encapsulation efficiency were 5.04 mV, 91.21 and 98.38% respectively. Micelles demonstrated sustained release of PBG. Micelles caused a 2.1-fold enhancement in vitro antitumor activity of PBG towards MCF-7 cells. Micelles proved safe for intravenous injection as PBG was stable at high pH; micelle size and encapsulation efficiency were retained upon dilution. CONCLUSION: Developed mixed micelles proved potential nanocarriers for PBG in cancer chemotherapy.

Novel solvent-free gelucire extract of Plumbago zeylanica using non-everted rat intestinal sac method for improved therapeutic efficacy of plumbagin.

INTRODUCTION: Various shortcomings of the available methods of extraction of plumbagin from Plumbago zeylanica using non-edible organic solvents coupled with the poor aqueous solubility and low bioavailability called for extracting plumbagin in a water soluble form via a single step technique using hydrophilic lipid Gelucire 44/14. METHODS: Gelucire extract of P. zeylanica (GPZ) was prepared and evaluated for extraction efficiency, High-performance thin layer chromatography (HPTLC) and thermal analysis. In vitro intestinal absorption and bioavailability of plumbagin from GPZ in comparison with that of aqueous (APZ), ethanolic extract (EPZ) and standard plumbagin studied using non-everted rat intestinal sac model. RESULTS: The GPZ showed significantly higher extraction efficiency (3.24±0.12% w/w) compared to ethanolic (EPZ) and aqueous (APZ) extraction, 2.48±0.16% w/w and 0.07±0.02% w/w respectively. GPZ displayed significantly higher Q(30min) (cumulative percentage absorption of plumbagin in 30 min) and lower t(40%) (time required for 40% w/w drug absorption). The flux and apparent permeability coefficient in duodenum and ileum were 2, 3 and 6 fold higher than EPZ, standard plumbagin and APZ respectively. DISCUSSION: Improved therapeutic efficacy of plumbagin may be due to the micellar solubilization and consequent enhanced partitioning of plumbagin through intestinal by Gelucire which was reflected in the in vivo anti-inflammatory study conducted in rats. CONCLUSION: Thus extraction using Gelucire can be proclaimed as an efficient, economic and solvent-free technique for extraction of plumbagin and can be utilized for various clinically important water insoluble phytoconstituents in order to improve their biopharmaceutical properties.

Development of photostable gastro retentive formulation for nifedipine using low-density polypropylene microporous particles.

The aim of this study was to develop photostable gastro retentive formulation for nifedipine loading into low-density polypropylene microporous particles (Accurel MP 1000®) by a solvent evaporation technique using the 3² factorial design. Yield, drug loading, surface topography, thermal properties, crystal characteristics, photostability and in vitro drug release were studied. Optimized microparticles formulated into a capsule were evaluated for the dissolution study and compared with marketed formulation. Higher values of T(50%), time required for 50% degradation of drug with threefold and 1.5-fold decrease in degradation rate constant (K) under UV and fluorescent lamp were observed for the microparticles, respectively, as compared to pure nifedipine indicated remarkable improved photostability. Microparticles showed good floating ability in 0.1N HCl with initial burst release (16-29%) followed by the zero-order drug release up to 8 h. The capsule formulation followed the ideal modified release pattern.