Experimental design, formulation and in vivo evaluation of a novel topical in situ gel system to treat ocular infections.

In situ gels have been extensively explored as ocular drug delivery system to enhance bioavailability and efficacy. The objective of present study was to design, formulate and evaluate ion-activated in situ gel to enhance the ocular penetration and therapeutic performance of moxifloxacin in ophthalmic delivery. A simplex lattice design was utilized to examine the effect of various factors on experimental outcomes of the in situ gel system. The influence of polymers (independent variables) such as gellan gum (X1), sodium alginate (X2), and HPMC (X3) on gel strength, adhesive force, viscosity and drug release after 10 h (Q10) were assessed. Selected formulation (MH7) was studied for ex vivo permeation, in vivo irritation and pharmacokinetics in rabbits. Data revealed that increase in concentration of polymers led to higher gel strength, adhesive force and viscosity, however, decreases the drug release. MH7 exhibited all physicochemical properties within acceptable limits and was stable for 6 months. Release profile of moxifloxacin from MH7 was comparable to the check point batches and followed Korsmeyer-Peppas matrix diffusion-controlled mechanism. Ocular irritation study signifies that selected formulation is safe and non-irritant for ophthalmic administration. In vivo pharmacokinetics data indicates significant improvement of moxifloxacin bioavailability (p < 0.0001) from MH7, as evidenced by higher Cmax (727 ± 56 ng/ml) and greater AUC (2881 ± 108 ng h/ml), when compared with commercial eye drops (Cmax; 503 ± 85 ng/ml and AUC; 978 ± 86 ng h/ml). In conclusion, developed in situ gel system (MH7) could offers a more effective and extended ophthalmic therapy of moxifloxacin in ocular infections when compared to conventional eye drops.

The Beneficial Effect of Boswellic Acid on Bone Metabolism and Possible Mechanisms of Action in Experimental Osteoporosis.

Estrogen is instrumental in the pathological process of osteoporosis because a deficiency of this hormone increases the release of bone-resorbing cytokines. Acetyl-11-keto-ß-boswellic acid (AKBA), a constituent from Boswellia serrata, has an anti-inflammatory effect by inhibiting tumor necrosis factor-α (TNF-α) expression, which leads to a decline in receptor activator of nuclear factor-kappa B (NF-κB) ligand, and consequently, a reduction in osteoclast activity. Hence, AKBA may be beneficial against bone loss during osteoporosis. Therefore, the current study intended to evaluate the beneficial effects of AKBA in ovariectomy-induced osteoporosis and to investigate its mechanism of action. Sham-operation or ovariectomy female Sprague Dawley rats were used for evaluating the antiosteoporotic effect of AKBA in this study. AKBA (35 mg/kg, p.o.) and estradiol (0.05 mg/kg, i.m.) were administered for 42 days. At the end of the experiment, body and uterus weights, serum and urine calcium and phosphorus, serum alkaline phosphatase, and urinary creatinine levels, besides serum levels of NF-κB and TNF-α were determined. Weight, length, thickness, hardness, calcium content, as well as the bone mineral density of femur bone and lumbar vertebra were measured. A histopathological examination was also carried out. AKBA ameliorated all tested parameters and restored a normal histological structure. Thus, AKBA showed good antiosteoporotic activity, which may be mediated through its suppression of the NF-κB-induced TNF-α signaling pathway.

Preparation and evaluation of niosome gel containing acyclovir for enhanced dermal deposition.

Niosomes suggest a versatile vesicle delivery system with possible transport of drugs via topical route for skin delivery. The aim of the present research was to optimize niosome gel formulation of acyclovir and to evaluate in both in vitro and in vivo rabbit model. Niosome formulations were formulated by coacervation phase separation technique with different ratios of nonionic surfactants, phospholipids and cholesterol using 32 factorial design. Altering the surfactant concentration has influenced the drug entrapment, but not vesicle size. At high surfactant combinations, the acyclovir release from niosomes was strongly influenced by cholesterol:lecithin ratio. Ex vivo drug permeation data indicate substantial difference in flux values and was influenced by the niosome composition. Ex vivo studies using formulation (B8) for drug deposition indicate greater amount of niosome being diffused into the skin layers and formed a depot, compared to commercial acyclovir cream (control). Two distinct dermatopharmacokinetic profiles were observed, in vivo, for niosome gel formulation (B8) and control, which were analog to the profiles observed with ex vivo deposition studies. In vivo plasma drug level suggests low systemic exposure of acyclovir (Cmax: 9.44 ± 2.27 ng/mL and 14.54 ± 3.11 ng/mL for niosome formulation and control, respectively). Comparison of kinetic data of acyclovir in the stratum corneum and plasma signifies that the niosome formulation forms a depot in the epidermis or dermis region. This study concludes that the niosome gel formulation (B8) could be a viable vesicular system for an impressive transdermal delivery of acyclovir by topical application.

Assessment of pharmacokinetic interaction of spirulina with glitazone in a type 2 diabetes rat model.

The objective of the current study was to assess the possible pharmacokinetic interactions of spirulina with glitazones in an insulin resistance rat model. Wistar male albino rats were equally divided into five groups: insulin resistant rats+spirulina (500 mg/kg)+pioglitazone (10 mg/kg), insulin resistant rats+pioglitazone (10 mg/kg), insulin resistant rats+spirulina (500 mg/kg)+rosiglitazone (10 mg/kg), insulin resistant rats+rosiglitazone (10 mg/kg), and insulin resistant rats+spirulina (500 mg/kg). Described doses of pioglitazone, rosiglitazone, or spirulina were per orally administered and the plasma drug concentrations were determined. The pharmacokinetic parameters such as Tmax, Cmax, AUC(0-α), t1/2, and Kel were determined by plotting the drug concentration as a function of time. The data observed in this acute study indicated that there was no statistically significant difference in any of the pharmacokinetic parameters (Tmax, Cmax, AUC(0-α), t1/2, and Kel) of glitazones (pioglitazone, rosiglitazone) or spirulina, when they were coadministered. Given the promising results, this study concludes that the coadministration of spirulina does not influence the pharmacokinetics of glitazones in a type 2 diabetes rat model. Further chronic in vivo studies are recommended to assess the real time effect.