Furthermore, NEs can be formulated with little energy input (heat or mixing), have a long shelf life, and is characterized with simplicity of scale up of the manufacturing process ( 14). Nanoemulsion (NE) possesses droplet size generally in the range of 10–100 nm but in contrast to SMEDDS, it employs a lesser amount (5–10%) of surfactant. One of the approaches to circumvent these limitations is to deliver hydrophobic therapeutic agents in the form of a nanoemulsion formulation that like SMEDDS is also isotropic, thermodynamically stable, transparent (or translucent) system of oil, water, and surfactants. Furthermore, precipitation of the hydrophobic therapeutic agent formulated as SMEDDS and encapsulated in gelatin capsule may occur due to propensity of the volatile solvents used in formulation of SMEDDS to get transferred to the shell ( 13). SMEDDS as a delivery system have been reported to employ high concentration (30–60%) of surfactants that may lead to cellular toxicity ( 12). ![]() OLM has been formulated as a self-microemulsifying drug delivery system (SMEDDS) using capryol 90, tween 20 and tetraglycol (10:60:30, v/ v/ v) and Lee and his coworkers reported an improved relative bioavailability of 170% compared to the suspension in male Sprague–Dawley rats ( 11). Non-ionic surfactants such as Tween 80 have been stated to be valuable pharmaceutical excipient in order to prevent the function of the drug-resistant P-glycoprotein (P-gp) efflux pump and thus augment the intestinal absorption of therapeutic agents susceptible to P-gp-mediated efflux in the intestine ( 10). Oil to water nanoemulsion systems are reported to augment aqueous solubility of hydrophobic therapeutic agents by including them in the oil phase of the nanoemulsion ( 7– 9). Poor aqueous solubility and efflux of hydrophobic therapeutic agents by means of drug resistance pump in the gastrointestinal tract contribute to their low bioavailability ( 5, 6). OLM is highly lipophilic in nature (log p = 4.31) which attributes to its low aqueous solubility. Commercially available tablets of OLM exhibit reduced oral absorption leading to low oral bioavailability of 25.6% ( 4). Olmesartan is reported to be more helpful in patients with essential hypertension in comparison to other angiotensin II receptor blockers with respect to decrease in ambulatory blood pressure ( 3). By the action of aryl esterases, situated in both intestine and plasma, it gets quickly de-esterified upon oral administration in to an active metabolite, i.e., olmesartan ( 2). Olmesartan medoxomil (OLM) is an extensively used antihypertensive drug ( 1). The present study established capsulated surface-adsorbed NE as a viable delivery system with the potential to overcome the handling limitations of NE. ![]() Conversion of NE to surface-adsorbed NE and its reconstitution to NE did not affect the in vitro release profile of OLM as the similarity factor with respect to NE was found to be 66% and 73% respectively. F3 was adsorbed over colloidal silicon dioxide (2 ml/400 mg) to produce free-flowing solid surface-adsorbed NE that presented a ready-to-fill capsule composition. Formulation (F3) comprising of Capmul MCM® (10% v/ v), Tween 80® (11.25% v/ v), polyethylene glycol 400 (3.75% v/ v), and double-distilled water (75% v/ v) displayed highest percentage cumulative drug release (%CDR 96.69 ± 1.841), least globule size (17.51 ± 5.87 nm), low PDI (0.203 ± 0.032), high zeta potential (−58.93 ± 0.98 mV), and hence was selected as the optimized formulation. Rationally selected NE formulations were evaluated for percentage transmittance, viscosity, refractive index, globule size, zeta potential, and polydispersity index (PDI). ![]() Selection of oil, surfactant, and cosurfactant for construction of pseudoternary phase diagrams was made on the basis of solubility of drug in these excipients. The present study aimed at development of capsular dosage form of surface-adsorbed nanoemulsion (NE) of olmesartan medoxomil (OLM) so as to overcome the limitations associated with handling of liquid NEs without affecting their pharmaceutical efficacy.
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