Study of physicochemical properties of flutamide-loaded Ocimum basilicum microspheres with ex vivo mucoadhesion and in vitro drug release

Drug which shows extensive first pass effect is difficult task that, needs to be solved by formulators in the pharmaceutical science. The low oral bioavailability (49%) of flutamide may be due to poor wettability, low aqueous solubility and extensive first pass effect. The aim of present investigation was to prepare flutamide loaded microspheres and incorporate it into suppositories for rectal delivery to avoid first pass effect and enhance residence time. Flutamide loaded mucoadhesive microspheres of Ocimum Basilicum mucilage (OBM) were prepared using spray drying and characterized by percent production yield, encapsulation efficiency, particle size, zeta potential, polydispersity index, DSC, SEM, XRPD, in vitro drug release and stability studies. Moreover, ex vivo mucoadhesion was investigated using falling liquid film technique to determine the adhesion of microspheres to sheep rectal mucosa. The microspheres had nearly spherical shape and size about 2.53?μm. The encapsulation efficiency and mucoadhesion of optimized formulation MBF10 were found to be 69.6?±?2.3% and 89.01?±?2.18%, respectively. Percent CDR of optimized flutamide loaded mucoadhesive microspheres was found to be 88.7?±?1.3 at 7?h. In conclusion, OBM microparticles based suppository could be used to deliver drug through rectal delivery.     

Floating modular drug delivery systems with buoyancy independent of release mechanisms to sustain amoxicillin and clarithromycin intra-gastric concentrations

Release modules of amoxicillin and clarithromycin combined in a single dosage form designed to float in the gastric content and to sustain the intra-gastric concentrations of these two antibiotics used for the eradication of Helicobacter pylori have been studied. The modules having a disc shape with curved bases were formulated as hydrophilic matrices. Two modules of clarithromycin were assembled by sticking the concave base of one module to the concave base of the other, creating an internal void chamber. The final dosage form was a floating assembly of three modules of clarithromycin and two of amoxicillin in which the drug release mechanism did not interfere with the floatation mechanism. The assembled system showed immediate in vitro floatation at pH 1.2, lasting 5?h. The in vitro antibiotics release profiles from individual modules and assembled systems exhibited linear release rate during buoyancy for at least 8?h. The predicted antibiotic concentrations in the stomach maintained for long time levels significantly higher than the respective minimum inhibitory concentrations (MIC). In addition, an in vivo absorption study performed on beagle dogs confirmed the slow release of clarithromycin and amoxicillin from the assembled system during the assembly’s permanence in the stomach for at least 4?h.     

Colonic drug delivery: influence of cross-linking agent on pectin beads properties and role of the shell capsule type

For colonic delivery, pectin beads obtained by ionotropic gelation method have been already reported as an interesting approach. This study investigated the influence of the cross-linking agent (calcium or zinc) and the type of shell capsule used (classical or enteric capsules) on pectin beads properties and on their performance to target the colon (in vitro dissolution studies with subsequent pH change to mimic overall gastro-intestinal tract). Zinc pectinate beads seemed to be relatively similar to calcium's ones in morphological point, except on the surface aspect. When beads were introduced in classical hard capsules, ketoprofen release was not significantly different between CPG and ZPG beads, and it was too premature and too quick due to a chemical erosion of the pectinate matrix (acid + basic attacks). However, zinc pectinate beads showed slower ketoprofen release compared with calcium pectinate beads when enteric hard capsules were used. This interesting finding could be due to the strength of the network formed during the process between the zinc cations and the LM-pectin following the “egg-box” model. This network was stronger and induced a reduction of swelling and hydration when contact with dissolution medium, then subsequently a decrease of drug release. Thus, the zinc pectinate beads could protect sufficiently drug entrapped from the upper gastro-intestinal conditions and drug release will be controlled by pectin degradation with colonic microflora. Finally, these zinc pectinate beads in enteric hard capsules are promising as a carrier for specific colonic delivery of drugs after oral administration.     

Alginate-based in situ gelling suspensions and emulsions comprising N4-alkyloxycarbonyl derivatives of cytosine: zero-order release and effect of physicochemical properties

As an alternative to incorporation of various excipients, N⁴-alkyloxycarbonyl-cytosine derivatives possessing various physicochemical properties and cytosine regeneration rates have been examined to modify release rate and kinetics from in situ gelling alginate formulations, e.g., liquid formulations that gel in acidic gastric juice and release the entrapped derivative or parent cytosine. Linear relationships were obtained between the release rate constants and the square root of the solubility for suspension formulations. Calculated diffusion coefficients were observed to be similar for suspension and solution formulations; however, for in situ gelling emulsion formulations, diffusivity correlated linearly to log P. Zero-order release of parent cytosine was observed from in situ gelling suspensions of the poorly soluble acid-labile N⁴-adamantyloxycarbonyl-cytosine prodrug.     

The impact of preparation parameters on typical attributes of chitosan-heparin nanohydrogels: particle size,loading efficiency,and drug release

Today, developing an optimized nanoparticle (NP) preparation procedure is of paramount importance in all nanoparticulate drug delivery researches, leading to expanding more operative and clinically validated nanomedicines. In this study, a one-at-a-time experimental approach was used for evaluating the effect of various preparation factors on size, loading, and drug release of hydrogel NPs prepared with ionotropic gelation between heparin and chitosan. The size, loading efficiency (LE) and drug release profile of the NPs were evaluated when the chitosan molecular weight, chitosan concentration, heparin addition time to chitosan solution, heparin concentration, pH value of chitosan solution, temperature, and mixing rate were changed separately while other factors were in optimum condition. The results displayed that size and LE are highly influenced by chitosan concentration, getting an optimum of 63?±?0.57 and 75.19?±?2.65, respectively, when chitosan concentration was 0.75?mg/ml. Besides, heparin addition time of 3?min leaded to 74.1?±?0.79 % LE with no sensible effect on size and release profile. In addition, pH 5.5 showed a minimum size of 63?±?1.87, maximum LE of 73.81?±?3.13 and the slowest drug release with 63.71?±?3.84 % during one week. Although LE was not affected by temperature, size and release reduced to 63?±?0 and 74.21?±?1.99% when temperature increased from 25°C to 55°C. Also, continuous increase of mixer rate from 500 to 3500?rpm resulted in constant enhancement of LE from 58.3?±?3.6 to 74.4?±?2.59 as well as remarkable decrease in size from 148?±?4.88 to 63?±?2.64.     

Effect of particle size of calcium phosphate based bioceramic drug delivery carrier on the release kinetics of ciprofloxacin hydrochloride: an invitro study

Hydroxyapatite (HAP) is the constituent of calcium phosphate based bone cement and it is extensively used as a bone substitute and drug delivery vehicle in various biomedical applications. In the present study we investigated the release kinetics of ciprofloxacin loaded HAP and analyzed its ability to function as a targeted and sustained release drug carrier. Synthesis of HAP was carried out by combustion method using tartaric acid as a fuel and nitric acid as an oxidizer. Powder XRD and FTIR techniques were employed to characterize the phase purity of the drug carrier and to verify the chemical interaction between the drug and carrier. The synthesized powders were sieve separated to make two different drug carriers with different particle sizes and the surface topography of the pellets of the drug carrier was imaged by AFM. Surface area and porosity of the drug carrier was carried out using surface area analyzer. The in-vitro drug release kinetics was performed in simulated body fluid, at 37.3°C. The amount of ciprofloxacin released is measured using UV-visible spectroscopy following the characteristic λ_max of 278 nm. The release saturates around 450 h which indicates that it can be used as a targeted and sustained release carrier for bone infections.     

Continuous direct tablet compression: effects of impeller rotation rate,total feed rate and drug content on the tablet properties and drug release

Context: Continuous processing is becoming popular in the pharmaceutical industry for its cost and quality advantages.

Objective: This study evaluated the mechanical properties, uniformity of dosage units and drug release from the tablets prepared by continuous direct compression process.

Materials and methods: The tablet formulations consisted of acetaminophen (3–30% (w/w)) pre-blended with 0.25% (w/w) colloidal silicon dioxide, microcrystalline cellulose (69–96% (w/w)) and magnesium stearate (1% (w/w)). The continuous tableting line consisted of three loss-in-weight feeders and a convective continuous mixer and a rotary tablet press. The process continued for 8?min and steady state was reached within 5?min. The effects of acetaminophen content, impeller rotation rate (39–254?rpm) and total feed rate (15 and 20?kg/h) on tablet properties were examined.

Results and discussion: All the tablets complied with the friability requirements of European Pharmacopoeia and rapidly released acetaminophen. However, the relative standard deviation of acetaminophen content (10% (w/w)) increased with an increase in impeller rotation rate at a constant total feed rate (20?kg/h). A compression force of 12?kN tended to result in greater tablet hardness and subsequently a slower initial acetaminophen release from tablets when compared with those made with the compression force of about 8?kN.

Conclusions: In conclusion, tablets could be successfully prepared by a continuous direct compression process and process conditions affected to some extent tablet properties.