Evaluation of Tadalafil Nanosuspensions and Their PEG Solid Dispersion Matrices for Enhancing Its Dissolution Properties

Abstract

The aim of this work was to prepare and evaluate Tadalafil nanosuspensions and their PEG 4000 solid dispersion matrices to enhance its dissolution rate. Nanosuspensions were prepared by precipitation/ultrasonication technique at 5°C where different stabilizers were screened for stabilization. Nanosuspensions were characterized in terms of particle size and charge. Screening process limited suitable stabilizers into structurally related surfactants composed of a mixture of Tween80 and Span80 at 1:1 ratio (in percent, weight/volume) in adjusted alkaline pH (named TDTSp-OH). The surfactant mixture aided the production of nanosuspensions with an average particle size of 193 ± 8 nm and with short-term stability sufficient for further processing. Solid dispersion matrices made of dried Tadalafil nanosuspensions or dried Tadalafil raw powder suspensions and PEG 4000 as a carrier were prepared by direct compression. Drying was performed via dry heat or via freeze dry. Drug release studies showed that, in general, tablet formulations made of freeze-dried product exhibited faster initial release rates than the corresponding tablets made of oven-dried products which could be attributed to possible larger crystal growth and larger crushing strengths of oven-dried formulations. At best, 60% of drug was released from solid dispersion matrices, while more than 90% of drug was released from TDTSp-OH nanosuspension within the first 5 min. In conclusion, Tadalafil nanosuspensions obtained using a mixed surfactant system provided rapid dissolution rates of Tadalafil that can theoretically enhance its bioavailability.

Dissolution enhancement of tadalafil by liquisolid technique

“…However, suffering from poor aqueous solubility, tadalafil is a BCS class II drug. Numerous approaches for enhancing its dissolution rate were reported including the use of solid dispersions 29 , complexation with cyclodextrins 30 , inclusion in microporous silicas 31 , formulation of nanosuspensions 32 , use of self-nanoemulsifying drug delivery systems (SNEDDS) 33 , and nanostructured lipid carriers (NLCs) 34 . However, to the best of our knowledge, liquisolid technique has never been utilized to promote the dissolution of tadalafil in the reported literatures.…”

Physicochemical properties of tadalafil solid dispersions – Impact of polymer on the apparent solubility and dissolution rate of tadalafil

“…Poor solubility in water is a limiting factor for its 90 absorption leading to significant differences in the pharmacologi-91 cal response. Several methods have been already investigated for 92 Td solubility enhancement including cyclodextrin complexation 93 [1], preparation of nanoparticles [16] and self-nanoemulsifying 94 drug delivery systems [4]. In our previous study the amorphous 95 form of Td was obtained using several commercially available 96 amorphization techniques [25].…”

Response Surface Methodology for Optimization of Process Variables of Atorvastatin Suspension Preparation by Microprecipitation Method Using Desirability Function

“…According to Table 6 and Figure 6, the released drug in the fifth minute of the micronized AT formulations was compared with the pure (untreated) powder (P<0.05).The release rate of hydrophilic micronized particles is more than that of the hydrophobic particles of AT (P<0.05). 44 On the other hand, the dissolution efficiency of the micronized formulation (≈100%) was higher than pure powder (47.44%). All of the prepared formulations had no similarity with pure powder (f1>15).…”