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In-Vitro In-Vivo Correlation (IVIVC) of Inhaled Products Using Twin Stage Impinger
Al Ayoub, Y. Buzgeia, Asma Almousawi, Ghadeer Mazhar, H.R.A. Alzouebi, B. Gopalan, Rajendran C. Assi, Khaled H.
Al Ayoub, Y.
Buzgeia, Asma
Almousawi, Ghadeer
Mazhar, H.R.A.
Alzouebi, B.
Gopalan, Rajendran C.
Assi, Khaled H.
Publication Date
2022-02
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© 2021 Elsevier. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.
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openAccess
Accepted for publication
2021-09-16
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Abstract
In vitro dissolution testing as a form of quality control has become a necessity in the pharmaceutical industry.
As such, the need to establish a method that investigates the in vitro dissolution profile of inhaled products
should be taken into account. The prime focus in this study was to examine the in-vitro in-vivo correlation
utilising a modified version of the Twin Stage Impinger and to promote an in vitro dissolution model by
enhancing the Fine Particle Dose (FPD) collection method for dry powder inhalers.
The Twin Impinger was modified by inserting a stainless steel membrane holder disk in the base of the lower
chamber. The design, with optimum drug deposition, was adopted for the dissolution study of budesonide
and salbutamol. Afterwards, the membrane holder system was placed in the bottom of the dissolution vessel.
Phosphate buffer saline (PBS), simulated lung fluid (SLF, Gamble solution) and Phosphate buffer (PB) were
used in the study. The paddle dissolution apparatus, containing 300 mL of the medium, was operated at
75 rpm paddle speed. Samples were collected at defined time intervals and analysed using a validated HPLC
method.
The largest proportion of the budesonide dose was dissolved in PBS compared to PB and SLF. This was due to
the presence of surfactant (0.2% w/v polysorbate), which enhances the wettability and the solubility of the
poorly soluble drug (budesonide). The similarity factors for PBS and PB were 47.6 and 69.7, respectively,
using SLF as a reference, whereas the similarity factor for salbutamol dissolution between PB and SLF was
81.3, suggesting PB is a suitable substitute. Comparison using both the predicted and actual in vivo pharmacokinetics (PK) values of the two drugs, as well as the pattern of their Concentration-Time (c-t) profiles,
showed good similarity, which gave an indication of the validity of this in vitro dissolution method.
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Citation
Al Ayoub Y, Buzgeia A, Almousavi G et al (2021) In-Vitro In-Vivo Correlation (IVIVC) of Inhaled Products Using Twin Stage Impinger. Journal of Pharmaceutical Sciences. 111(2): 395-402.
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