Penetration enhancer-containing spanlastics (PECSs) for transdermal delivery of haloperidol: in vitro characterization, ex vivo permeation and in vivo biodistribution studies

Abstract

Haloperidol (Hal) is one of the widely used antipsychotic drugs. When orally administered, it suffers from low bioavailability due to hepatic first pass metabolism. This study aimed at developing Hal-loaded penetration enhancer-containing spanlastics (PECSs) to increase transdermal permeation of Hal with sustained release. PECSs were successfully prepared using ethanol injection method showing reasonable values of percentage entrapment efficiency, particle size, polydispersity index and zeta potential. The statistical analysis of the ex vivo permeation parameters led to the choice of F1L – made of Span® 60 and Tween® 80 at the weight ratio of 4:1 along with 1% w/v Labrasol® – as the selected formula (SF). SF was formulated into a hydrogel by using 2.5% w/v of HPMC K4M. The hydrogel exhibited good in vitro characteristics. Also, it retained its physical and chemical stability for one month in the refrigerator. The radiolabeling of SF showed a maximum yield by mixing of 100 µl of diluted formula with 50 µl saline having 200 MBq of 99mTc and containing 13.6 mg of reducing agent (NaBH4) and volume completed to 300 µl by saline at pH 10 for 10 min as reaction time. The biodistribution study showed that the transdermal 99mTc-SF hydrogel exhibited a more sustained release pattern and longer circulation duration with pulsatile behavior in the blood and higher brain levels than the oral 99mTc-SF dispersion. So, transdermal hydrogel of SF may be considered a promising sustained release formula for Hal maintenance therapy with reduced dose size and less frequent administration than oral formula.

Sustained ocular delivery of Dorzolamide-HCl via proniosomal gel formulation: in-vitro characterization, statistical optimization, and in-vivo pharmacodynamic evaluation in rabbits

“…It was also reported that the shear stress causes the release of some of the entrapped water from the dispersed polymer molecules. This leads to decrease in their apparent molecular weight and concentration (Fahmy et al., 2018 ).…”

“…Similarity factor (f 2 ) was calculated to compare the release profiles of the OF-gel before and after sterilization via the following equation (Moore & Flanner, 1996 ; Fahmy et al., 2018 ): where n is the number of sampling points, R t and T t are the mean percent released from reference (before sterilization) and from test (after sterilization) at time t respectively. An f 2 value greater than or equal to 50 indicates that the release profiles are similar, whereas values less than 50 indicate dissimilarity of release profiles.…”

“…Rheological data was fitted to the non-Newtonian Bingham’s, Carreau’s and Casson’s models to examine the pattern of flow. The model with the highest R 2 value described the flow pattern of OF-gel (Fahmy et al., 2018 ).…”

<p>Formulation of Nanospanlastics as a Promising Approach for ‎Improving the Topical Delivery of a Natural Leukotriene Inhibitor (3-‎Acetyl-11-Keto-β-Boswellic Acid): Statistical Optimization, in vitro ‎Characterization, and ex vivo Permeation Study</p>

“…36 In vitro Characterization of AKBA-Loaded SNVs Determination of Drug Content and Entrapment Efficiency of AKBA-Loaded SNVs Methanol was selected as an appropriate solvent for the disruption of the prepared SNVs for the determination of total drug content. 31 Total drug contents (unentrapped+entrapped) of the prepared formulations were determined by dissolving 0.2 mL of nanospanlastic dispersion in methanol (25 mL) and then measuring drug content using a validated HPLC method at 260 nm. The entrapment efficiency percent (EE %) of AKBAloaded SNVs was estimated by the indirect method using ultracentrifugation to separate the un-entrapped drug.…”

“…The estimation of vesicle size and PDI was performed using a NICOMP 380 ZLS Zeta Potential/Particle Sizer (PSS Nicomp, Santa Barbara, CA, USA) at 25°C with a scattering angle of 90°. 13,31 Statistical Optimization of AKBA-Loaded SNVs Desirability values were determined to choose the optimized formula. 39 The desirability value lies between 0 and 1 and it describes the closeness of different responses to their ideal values.…”