Physicochemical properties of direct compression tablets with spray dried and ball milled solid dispersions of tadalafil in PVP-VA

Eur J Pharm Biopharm. 2016 Dec;109:14-23. doi: 10.1016/j.ejpb.2016.09.011. Epub 2016 Sep 20.

Abstract

The aim of this research was to develop immediate release tablets comprising solid dispersion (IRSDTs) of tadalafil (Td) in a vinylpyrrolidone and vinyl acetate block copolymer (PVP-VA), characterized by improved dissolution profiles. The solid dispersion of Td in PVP-VA (Td/PVP-VA) in a weight ratio of 1:1 (w/w) was prepared using two different processes i.e. spray drying and ball milling. While the former process has been well established in the formulation of IRSDTs the latter has not been exploited in these systems yet. Regardless of the preparation method, both Td/PVP-VA solid dispersions were amorphous as confirmed by PXRD, DSC and FTIR. However, different morphology of particles (SEM) resulted in differences in water apparent solubility and disk intrinsic dissolution rate (DIDR). Both solid dispersions and crystalline Td were successfully made into directly compressible tablets at three doses of Td, i.e. 2.5mg, 10mgand20mg, yielding nine different formulations (D1-D9). Each of the lots met the requirements set by Ph.Eur. and was evaluated with respect to appearance, diameter, thickness, mass, hardness, friability, disintegration time and content of Td. IRSDTs performed as supersaturable formulations and had significantly improved water dissolution profiles in comparison with equivalent tablets containing crystalline Td and the marketed formulations. Tablets with both spray dried and ball milled Td/PVP-VA revealed the greatest improvement in dissolution depending on the investigated doses, i.e. 2.5mgand20mg, respectively. Also, dissolution of Td from Td/PVP-VA delivered in different forms occurred in the following order: powders>tablets>capsules.

Keywords: Amorphous solid dispersion; Ball milling; Direct compression tablets; Dissolution; Spray drying; Supersaturable formulation; Tadalafil.

MeSH terms

  • Calorimetry, Differential Scanning
  • Compressive Strength
  • Crystallization
  • Desiccation
  • Drug Compounding / methods*
  • Drug Stability
  • Microscopy, Electron, Scanning
  • Powders
  • Pyrrolidines / chemistry*
  • Solubility
  • Spectrophotometry, Infrared
  • Spectroscopy, Fourier Transform Infrared
  • Tablets / chemistry*
  • Tadalafil / chemistry*
  • Vinyl Compounds / chemistry*
  • X-Ray Diffraction

Substances

  • Powders
  • Pyrrolidines
  • Tablets
  • Vinyl Compounds
  • poly(vinylpyrrolidone-co-vinyl-acetate)
  • Tadalafil