Development of High-Strength Extended-Release Multiparticulate System by Crystallo-co-agglomeration Technique with Integration of Central Composite Design.

The number of unit operations to be followed in the preparation of tablets was cumbersome and may introduce material as well as process-related critical parameters which may negatively affect the quality of final formulation. The hypothesis of the present research was to develop directly compressible, high-strength extended-release spherical agglomerates of talc containing indapamide by crystallo-co-agglomeration technique. Hydroxypropyl methylcellulose 15 cps and polyethylene glycol 6000 were used to impart the desired sphericity, strength, and deformability to agglomerates, respectively. Ethyl cellulose 10 cps was used to improve the strength of agglomerates and achieve extended release. Design of experiment (rotatable central composite design) was implemented for the elucidation of the effect of type and quantity of polymers on quality attributes of agglomerates. Prepared agglomerates were evaluated for morphological, micromeritic, mechanical, and drug release properties. A satisfactory yield (> 97%, wt/wt), better crushing strength, and low friability of agglomerates indicated good processing and handling characteristics. Compatibility and reduced crystallinity of indapamide in agglomerates were confirmed by spectroscopic and X-ray diffraction studies. Formation of the miniscular dosage form and hydrophobicity of talc were the key factors observed in controlling and extending the drug release (up to 6 h) from agglomerates. Hence, the developed crystallo-co-agglomeration technique could be successfully used for the preparation of directly compressible high-strength extended-release spherical agglomerates of indapamide.

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.

Preparation and evaluation of talc agglomerates obtained by wet spherical agglomeration as a substrate for coating.

The present research was aimed at the preparation of spherical agglomerates of talc (SAT) by wet spherical agglomeration (WSA) and evaluation as inert core/substrate for coating. Talc being an inert and inexpensive excipient was used in the design of spherical agglomerates. To evaluate agglomerate performance, comparison was made with sugar spheres (SS), having a size 1200 µm, for surface morphology, micromeritics, mechanical, compressional and drug release properties. Surface morphology studied by scanning electron microscopy (SEM) and optical profilometry have shown smooth surface of SAT compared to SS. Shape and sphericity analysis of both showed aspect ratio close to 1. Flowability of SAT was similar to SS. Although, crushing force of SAT was significantly less than SS (p = 0.05), friability studies revealed that it was satisfactory. Compressibility studies showed plastic deformation of SAT unlike SS. Both SAT and SS had comparable drug and polymer layering efficiency, with better surface smoothness in SAT than SS, as confirmed from optical profilometry. Thus, SAT, similar to SS, can be used as a substrate for coating due to its comparable surface topography, micromeritics, adequate crushing resistance and satisfactory drug and polymer layering efficiency.

Low density porous carrier drug adsorption and release study by response surface methodology using different solvents.

Low density porous carriers are widely used in the pharmaceutical applications. Response surface methodology, using 3(2) factorial design was used to study drug adsorption on and its release patterns from microporous polypropylene (Accurel MP 1000) in the absence of additives. Ibuprofen, as model drug, was adsorbed on the polymer by solvent evaporation using two organic solvents methanol (M) and dichloromethane (DCM). The amount of carrier (100 mg) and its particle size range (250-350 microm) were kept invariant while solvent volume (X1) and drug amount (X2) were taken as variables. Drug adsorption pattern depended on the type and amount of solvent used. DSC, XRD, FTIR and TGA, predict crystalline nature and physical form of adsorption. SEM showed the penetration and adsorption of the drug in and on the microporous polymer. Accurel MP 1000 had a pore volume of 1.992 g/cm3 and surface area of 55.9855 m2/g as detected by mercury porosimetery. On drug adsorption, pore volume ranged from 0.413 to 1.198 g/cm3 for methanol and 0.280-0.759 g/cm3 for DCM. Similarly surface area was in the range 38.445-25.497 m2/g for methanol and 18.710-32.528m2/g for DCM. The drug release was investigated in phosphate buffer pH 7.2. All batches showed excellent in vitro floating property. Drug release was partial with recovery to complete dependent on type and volume of solvent. R2 values relating to bulk density, pore volume, surface area and drug release at 60, 120 and 180 min were estimated. Effect of solvent properties shows a positive influence on drug adsorption and release. Release profiles of some batches could be considered as gastroretentive drug delivery system.

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.

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.

Evaluation of molecular pharmaceutical and in-vivo properties of spray-dried isolated andrographolide-PVP.

OBJECTIVES: Andrographolide, a natural lipophilic molecule, has a wide range of pharmacological actions. However, due to low aqueous solubility, it has low oral bioavailability. The purpose of the study was to increase the solubility and dissolution rate of isolated andrographolide by formulating its solid dispersion. METHOD: Solid dispersions were obtained by a spray-drying technique using different ratios of drug to polyvinylpyrrolidine (PVP K-30). Solid dispersions in compression with isolated drug and corresponding physical mixtures were characterized for various molecular pharmaceutical properties and subjected to stability study for up to 3 months. KEY FINDINGS: A five-fold increase in saturation solubility of andrographolide with higher values of Q(5 min) (cumulative percentage release in 5 min) and lower values of t(75%) (time required for 75% w/w drug release) for solid dispersion was observed in different dissolution mediums. This was attributed to the formation of amorphous nature and intermolecular hydrogen bonding between drug and PVP K-30. The stability study showed there to be no significant change in molecular pharmaceutical properties and dissolution profile over the period of 3 months. Moreover, the in-vivo study in Wistar albino rats also justified improvement in the therapeutic efficacy of andrographolide after solid dispersion. CONCLUSIONS: This study demonstrates the utility of solid dispersion to improve primary and secondary pharmaceutical properties of andrographolide using PVP K-30 as a carrier.