Tenoxicam-kollicoat IR binary systems: physicochemical and biological evaluation.
Tenoxicam (TNX) binary systems in Kollicoat IR (KL) matrix were prepared in different drug: polymer ratios using kneading and spray-drying method. The prepared binary systems were characterized for drug dissolution rate, differential scanning calorimetry (DSC), IR spectroscopy and x-ray diffractometry. The results showed that the drug dissolution rate was remarkably enhanced by incorporating it in the KL matrix either by kneading or spray-drying, and the dissolution rate was increased by decreasing the drug weight ratio. The DSc and x-ray studies revealed the presence of TNX in less crystalline or amorphous state in its-KL binary systems. Moreover, the spray-dried TNX-KL system in 1:4 ratio, that exhibited the faster dissolution rate, was formulated in oral disintegrating tablets (ODTs). The data indicated that a fast disintegration and higher drug dissolution rate was achieved in case of the ODTs containing the spray-dried form compared to the ODTS containing untreated drug or the commercial tablet (Epicotil). Also, the drug exhibited significantly (p < 0.01) faster onset of the anti-inflammatory analgesic activities in case of the ODTs containing the spray-dried form, that was superior to that observed with both the commercial tablet product and the ODTS containing untreated drug.
Rosuvastatin calcium nanoparticles: Improving bioavailability by formulation and stabilization codesign
Purpose Rosuvastatin calcium (ROSCa) is a poorly soluble drug with bioavailability not exceeding 20%. Decreasing the particle size may enhance its solubility, dissolution rate and bioavailability. Therefore, the aim of the current study is to prepare ROSCa nanoparticles by wet milling technique using planetary ball mill. The codesign between formulation and stabilization of nanoparticles was studied to achieve both high dissolution as well as bioavailability. Methodology ROSCa nanosuspensions was prepared by wet milling technique using planetary ball mill, by applying milling ball size of 0.1 mm at speed of 800 rpm for 3 cycles each cycle composed of 10 minutes. HPMC, PVP k-30, pluronic F-127, Tween 80 and PEG 6000 were used as stabilizers. The nanosuspensions were then freeze-dried, and the dried nanoparticles were evaluated for particle size, zeta potential, in-vitro dissolution test, XRPD and in-vivo study. Results ROSCa nanoparticles stabilized with 10% PVP (P3) had a good stability with smallest particle size, which in turn enhanced the dissolution rate. The particle size of the leading formula was 461.8 ± 16.68 nm with zeta potential of -31.8 ± 7.22 mV compared to untreated drug that has a particle size of 618μm. The percent of ROSCa dissolved after 1 hour enhanced significantly which reached 72% and 58.25% for leading nanoparticle formula and untreated ROSCa, respectively (P < 0.05). The in-vivo study of ROSCa from the leading nanoparticle formula showed a significant enhancement in the Cmax after 2 h (82.35 ng/ml) compared to 9.2 ng/ml for untreated drug. Conclusion Wet milling technique is a successful method to prepare ROSCa nanoparticles. From different stabilizer used, PVP (10%) was able to produce stable nanoparticle with small particle size which significantly enhance the dissolution rate and pharmacokinetics parameters of ROSCa.
Improved Skin Penetration Using In Situ Nanoparticulate Diclofenac Diethylamine in Hydrogel Systems: In Vitro and In Vivo Studies
Delivering diclofenac diethylamine transdermally by means of a hydrogel is an approach to reduce or avoid systemic toxicity of the drug while providing local action for a prolonged period. In the present investigation, a process was developed to produce nanosize particles (about 10 nm) of diclofenac diethylamine in situ during the development of hydrogel, using simple mixing technique. Hydrogel was developed with polyvinyl alcohol (PVA) (5.8% w/w) and carbopol 71G (1.5% w/w). The formulations were evaluated on the basis of field emission scanning electron microscopy, texture analysis, and the assessment of various physiochemical properties. Viscosity (163–165 cps for hydrogel containing microsize drug particles and 171–173 cps for hydrogel containing nanosize drug particles, respectively) and swelling index (varied between 0.62 and 0.68) data favor the hydrogels for satisfactory topical applications. The measured hardness of the different hydrogels was uniform indicating a uniform spreadability. Data of in vitro skin (cadaver) permeation for 10 h showed that the enhancement ratios of the flux of the formulation containing nanosize drug (without the permeation enhancer) were 9.72 and 1.30 compared to the formulation containing microsized drug and the marketed formulations, respectively. In vivo plasma level of the drug increased predominantly for the hydrogel containing nanosize drug-clusters. The study depicts a simple technique for preparing hydrogel containing nanosize diclofenac diethylamine particles in situ, which can be commercially viable. The study also shows the advantage of the experimental transdermal hydrogel with nanosize drug particles over the hydrogel with microsize drug particles.