Preparation of SLN-containing thermoresponsive in-situ forming gel as a controlled nanoparticle delivery system and investigating its rheological, thermal and erosion behavior

Various nanoparticles have been investigated as novel drug delivery systems, including solid lipid nanoparticles [SLNs]. Due to their rapid clearance from systemic circulation, nanoparticles do not provide sustained action in most cases. Different strategies have been employed to overcome this problem. In this direction, the present study introduces erodible insitu forming gel systems as potential vehicles for prolonged release of SLNs. SLNs were prepared by solidification of an oil-in-water microemulsion containing stearic acid, surfactants and co-surfactants. Nanoparticles were then dispersed in a thermosensitive Poloxamer 407 aqueous solution [sol] at 4[degree]C and their effects on gel forming ability, sol-gel transition and rheological behavior of the system were investigated over 5-50[degree]C. Thermal behavior of the system was investigated by differential scanning calorimetry too. Erosion rate of the gel in the presence and absence of SLN was measured by gravimetric method. Integrity of SLNs in the system was investigated by scanning electron microscopy [SEM] and particle size analysis. SLN showed particle size and zeta potential of 130 +/- 1.39 nm and - 44 +/- 2.1 mV respectively. Particle size analysis and SEM studies after gel erosion revealed presence of intact SLN in the hydrogel. SLN reduced erosion rate of Poloxamer gel and increased its sol-gel transition temperature from 26 to 29[degree]C. However, gelling kinetic did not change significantly after addition of SLN. Damping factor <1 indicated stability of the SLN-containing system. Present results indicate potential of sol-gel systems for controlled nanoparticle delivery and show that SLN affects properties of the system

Formulation, characterization and optimization of liposomes containing eicosapentaenoic and docosahexaenoic acids; a methodology approach

Omega-3 fatty acids [FAs] have been shown to prevent cardiovascular disease. The most commonly used omega-3 fatty acids like eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] are highly vulnerable to oxidation and therefore, have short shelf life. Recent advances in nanoliposomes provided a biocompatible system for stabilizing omega-3 FAs. Several methods could be implemented to prepare nanoliposomes. To the best of our knowledge, the performances of these methods in preparation omega-3 FAs have not been examined. Nanoliposomes were prepared by thin film hydration followed by one of the following methods: 1- extrusion, ultrasonic irradiation; 2- bath sonication; 3- probe sonication; or 4- combined probe and bath sonication. The size of liposomes obtained from methods 1 to 4 were 99.7 +/- 3.5, 381.2 +/- 7.8, 90.1 +/- 2.3, and 87.1 +/- 4.10 nm with zeta potential being -42.4 +/- 1,7,-36.3 +/- 1.6, -43.8 +/- 2.4, and 31.6 +/- 1.9 mV, respectively. The encapsulation efficiency [EE] for DHA was 13.2 +/- 1.1%, 26.7 +/- 1.9%, 56.9 +/- 5.2% and 51.8 +/- 3.8% for methods 1 to 4, respectively. The corresponding levels for EPA were 6.5 +/- 1.3%, 18.1 +/- 2.3%, 38.6 +/- 1.8%, and 38 +/- 3.7%, respectively. The EE for DHA and EPA of liposomes for both methods 3 and 4 increased significantly [p<0.05]. Propanal, as the major volatile product formed during liposomal preparations, amounts from 81.2 +/- 4.1 to 118.8 +/- 2.3 microg/Kg. The differential scanning calorimetry [DSC] study showed that DHA and EPA influence the phase transition temperature of small unilamellar vesicles [SUVs] of dipalmitoyl phosphatidyl choline [DPPC]. Transmission electron microscopy [TEM] images of liposomes stained with uranyl acetate showed that the liposomes were spherical in shape and maintain high structural integrity. In conclusion, probe ultrasound of pre-formed liposomes facilitates significant loading of DHA and EPA into the nanoliposomal membrane

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EMG needling is not a painless procedure. In recent studies it has been shown that a form of lidocaine has the efficacy which is similar to EMLA, for prevention of pain associated with EMG needling. The aim of this study was to evaluate the efficacy of Lidocaine H ointment in alleviating the pain caused by EMG needling. This study was performed on patients referred to Shohadaye Tajrish Hospital for EDx study in APR 2009- APR 2010. A double blinded, placebo controlled study was performed in 47 adult patients [94 lower limbs] to compare the pain of EMG needling into the tibialis anterior muscle after application of lidocaine-H ointment or placebo. Pain scores were obtained by using visual analog scale [VAS]. Experimental and placebo groups were compared with Mann-U-Whitney and Chi-square tests. The study was performed on 47 patients, 38.3% male and 61.7% female, mean age being 45.5 +/- 16.4years. Median VAS score was 4.66 +/- 2.14 vs. 6.11 +/- 2.07, [P<0.05]. 51.1% of patients in experimental group as compared to 21.3% in controls reported mild pain [VAS < 4], [P<0/01]. It seems that lidocaine-H ointment has beneficial effects in prevention of the pain associated with EMG needling

Preparation and characterization of theophylline-chitosan beads as an aapproach to colon delivery

Chitosan with excellent biodegradable and biocompatible characteristics has received attention as an oral drug delivery vehicle for controlled-release formulations. In this study an enteric-coated capsule containing theophylline-chitosan beads based on 2[3] factorial designs was prepared as a colon drug delivery system. The theophylline-chitosan gel beads were formulated by adding the drug-containing solution of chitosan into tripolyphosphate solutions, dropwise. The obtained beads were washed with water and freeze-dried before filling into the capsules. Eudragit[R] S100 was then used to enteric-coat the prepared capsules. Drug entrapment efficiency and the effects of different variables including: bead morphology, swelling behavior of the beads and the release behavior of the system on these parameters were investigated. Results showed that the highest and lowest swelling ratio is obtained at pH 4.5 and 7.2, respectively. These studies have shown that chitosan concentration and drug polymer weight ratio significantly affect the drug entrapment. Decreasing the drug solubility in external phase caused a significant increase in drug loading. External phase saturation with theophylline and tripolyphosphate, as well as decreasing temperature, have increased drug loading. Furthermore, the lowering of temperature had a significant effect on bead's hardness. The release of theophylline from freeze-dried beads filled in enteric-coated capsules was also investigated. Release of theophylline was prolonged with saturation of both drug and tripolyphosphate in the external phase. Results showed that the release of theophylline from chitosan beads is possibly due to more than one mechanism, possibly dissolution, diffusion and relaxation of the polymer chains

effect of hydroxyl containing tablet excipients on the adhesive duration of some mucoadhesive polymers

In order to investigate the effect of hydroxyl group containing tablet excipients on the duration of adhesion of mucoadhesive polymers, discs containing Carbopol 934 [C934], polycarbophil [PC], sodium carboxymethyl cellulose, hydroxypropylmethyl cellulose [HPMC], tragacanth [trag.] and sodium alginate [Na alg.], either alone or in the presence of various amounts of excipients were prepared. The duration of adhesion of the prepared discs were determined in pH 7.0 phosphate buffer at 37°C. All the excipients examined reduced the duration of adhesion and the relative durability of the polymer containing discs. HPMC discs despite showing the longest duration of mucoadhesion, suffered the greatest reduction in adhesive properties in the presence of excipients which were examined. Following HPMC, Na alg. and then trag. discs showed the greatest sensitivity to the presence of excipients. The least reduction in the duration of adhesion was observed with PC and C934. Among the excipients tested, spray-dried lactose produced the greatest reduction in the duration of adhesion, followed by polyethylene glycol 6000 and pregelatinized starch. The smallest reduction in the adhesive properties of the test polymers was due to talc powder. Hence, it seems that addition of the tablet excipients adversely reduce the adhesive properties of mucoadhesive dosage forms, which should be carefully considered during their formulation