Table 7.

Desired and achievable in vitro two-phase parameters to make dissolution test physiological for valproic acid, ondansetron, ibuprofen and felodipine based on in vivo properties and performance

	In vivo properties/ performance					In vitro drug properties			Desired in vitro parameters				Achievable in vitro parameters
	F a a	kaa × 104	Doseb	V c	Dose /V	clogD 6.5d	Dae × 106	PIf × 104	kpg × 104	AI/ Vah	F o, ∞ i	M T / V a j	Vessel capacity	Depth below impellerk	Vessel AI/Val	V a m	kpn × 104	V o o	β	Dosep
	Actual	Decon.	Theo.	Est.	Est.	Calc.	Est.	Est.	Based on ka	Est.		Based on dose/V		Based on USP standard		Req.	Est.	Req.		Req.
Drug name		s−1	mg	ml	mg/ml	-	cm2/s	cm/s	s−1	cm−1	-	mg/ml	ml	cm	cm−1	ml	s−1	ml	-	mg
Valproic acid (BCS II)	1	11.5	250	100	2.50	1.43	8.87	22.1	11.5	0.52	0.98	2.50	100	1.0	0.47	27	10.4	50	0.02	68
Ondansetron (BCS I or III)	1	5.3	8	100	0.08	1.65	6.63	18.4	5.3	0.29	0.98	0.08	1000 (USP II)	2.5	0.26	302	4.8	338	0.02	24
Ibuprofen (BCS II)	1	7.4	200	100	2.00	2.19	7.50	23.6	7.4	0.31	0.98	2.00	1000 (USP II)	2.5	0.26	302	6.1	97	0.02	604
Felodipine (BCS II)	1	12.5	5	100	0.05	3.41	6.10	20.3	12.5	0.62	0.98	0.05	Not possible unless depth below impeller is decreased to 2 cm and smaller vessel used

^aFrom reference [36].

^bArbitrarily chose one of the marketed oral unit doses.

^cAverage human fasted intestinal volume.

^dDetermined using reference [26].

^eEstimated using Hayduk-Laudie (H-L) method.

^fEstimated using Equation (10) assuming h_a = h_o = 30μm.

^gEqual to k_a.

^hCalculated using Equation (24).

ⁱValue should ideally be equal or close to Fa in vivo. 0.98 was chosen due to vessel size constraints.

^jEqual to Dose/V.

^kThe standard set-up for distance from bottom of vessel to bottom of impeller is 2.5 cm for the 1000 ml USP 2 vessel. 1 cm chosen for 100 ml vessel, which should accommodate a tablet or capsule.

^lFrom Table 1. Value set by apparatus geometry and minimum or maximum practical volume of media.

^mVolume required to achieve A_I/V_a.

ⁿEqual to estimated P_I times the actual A_I/V_a.

^oVolume required to achieve desired F_o,∞ based on cLogD 6.5 and V_a.

^pEqual to desirable M_T/V_a* achievable V_a.