Development, Characterization and Evaluation of Ritonavir Nanosuspension Treatment of Antiretroviral Therapy

Oral nanosuspension of ritonavir was prepared by antisolvent precipitation method using various polymers such as Eudragit RS100, Poloxamer 407, SLS and Methanol.The effect of eudragit RS100 and poloxamer 407 used stabilizer and SLS is surfactant was investigated on particle size and distribution, drug content, entrapment efficiency was observed. Ritonavir is having low solubility and low permeability drug belonging to class-IV according to BCS. Drug-excipient compatibility and amorphous nature of ritonavir drug is prepared nanosuspension was confirmed by FTIR, DSC and Motic microscope studies, respectively. The nanosuspension was further evaluated for drug content, saturation solubility study and entrapment efficiency. The average particle size of ritonavir nanaosuspensions formulas was observed from 0.006 µm to 0.017 µm. The studied in the solubility and dissolution rate there are the increase solubility and dissolution rate of ritonavir nanosuspension.

A Systematic Approach to the Development of Cilostazol Nanosuspension by Liquid Antisolvent Precipitation (LASP) and Its Combination with Ultrasound

Nanosizing is an approach to improve the dissolution rate of poorly soluble drugs. The first aim of this work was to develop nanosuspension of cilostazol with liquid antisolvent precipitation (LASP) and its combination with ultrasound. Second, to systematically study the effect of bottom-up processing factors on precipitated particles’ size and identify the optimal settings for the best reduction. After solvent and stabilizer screening, in-depth process characterization and optimization was performed using Design of Experiments. The work discusses the influence of critical factors found with statistical analysis: feed concentration, stabilizer amount, stirring speed and ultrasound energy governed by time and amplitude. LASP alone only generated particle size of a few microns, but combination with ultrasound was successful in nanosizing (d10 = 0.06, d50 = 0.33, d90 = 1.45 µm). Micro- and nanosuspension’s stability, particle morphology and solid state were studied. Nanosuspension displayed higher apparent solubility than equilibrium and superior dissolution rate over coarse cilostazol and microsuspension. A bottom-up method of precipitation-sonication was demonstrated to be a successful approach to improve the dissolution characteristics of poorly soluble, BCS class II drug cilostazol by reducing its particle size below micron scale, while retaining nanosuspension stability and unchanged crystalline form.

Preparation and Pharmacokinetic Characterization of an Anti-Virulence Compound Nanosuspensions

Antibiotic resistance has become a worldwide public health threat due to the rapid evolution and spread of antibiotic-resistant bacteria. CCG-211790 is a novel anti-virulence compound that does not kill bacteria but could ameliorate human diseases by inhibiting expression of virulence factors, thereby applying less selection pressure for antibiotic resistance. However, its potential clinical use is restricted because of its poor aqueous solubility, resulting in formulation challenges. Nanosuspension technology is an effective way to circumvent this problem. Nanosuspensions of CCG-211790 with two different particle sizes, NanoA (315 ± 6 nm) and NanoB (915 ± 24 nm), were prepared using an antisolvent precipitation-ultrasonication method with Tween 80 as the stabilizer. Particle and pharmacokinetics (PK) of CCG-211790 nanosuspensions were characterized. Both NanoA and NanoB demonstrated remarkable increases in dissolution rate compared with the bulk compound. The PK parameters of NanoA were comparable to those of CCG-211790 solution formulation in intravenous or oral administration, suggesting that CCG-211790 nanosuspensions with smaller particle size improved oral bioavailability and drug exposure compared to traditional formulations of drug candidates.

Resveratrol Nanocrystal Loaded Orodispersible Films: Formulation Development and In Vitro Characterization

Nanocrystals are a feasible system to improve the aqueous solubility of poorly soluble compounds. Orodispersible films (ODFs) offer a rapid release of the drug in the mouth and are preferred for patients with dysphagia or paediatrics. The objective of the current study was to develop resveratrol (RES) nanocrystal-loaded ODFs. RES nanocrystals were prepared by antisolvent precipitation in the existence of Poloxamer 188 as a polymeric stabilizer. Polyvinyl alcohol was used for the preparation of the ODFs by using the solvent casting method. Then, RES nanocrystals were incorporated into the films. Particle size (PS), polydispersity index (PDI), and zeta potential (ZP) values were measured for nanocrystals. ODFs were characterized, and bioadhesion, disintegration, and in vitro release studies were performed. RES nanocrystals were obtained with 631 nm PS, 0.314 PDI and − 14.3 ZP values. Over 90% of RES nanocrystals were loaded in ODFs, which were approximately 75 µm in thickness. The thermal and crystal properties of nanocrystals in ODFs were preserved regarding DSC and FTIR analyses. Homogenous distribution in smooth films was observed on SEM. Mechanical properties and bioadhesion forces were found to be appropriate for ODFs. The disintegration time was found below 30 seconds for nanocrystal loaded films. RES nanocrystal loaded film formulations showed > 85% release in 5 minutes, significantly higher (p < 0.05) than those prepared with coarse RES. Novel RES nanocrystal-loaded ODFs can be a promising delivery system for use as an antioxidant with improved patient compliance by increasing solubility and physical stability of RES.