Particle size reduction to the nanometer range: a promising approach to improve buccal absorption of poorly water-soluble drugs

Figures & data

Figure 1 Phenylephrine-containing buccal patch.

Table 1 Compositions of phenylephrine-containing microreservoirs (mg per microtablet)

Microtablet	Lactose	Mannitol	PVPP	CMS Na	PEG 6000	Aerosil	Phenylephrine	DNPE
PMT1	11.25	15	1.875	2.625	10.5	2.25	2.5
PMT2	11.25	12.5	1.875	2.625	10.5	2.25		5.0^a

Note:

a Equivalent to approximately 2.5 mg phenylephrine.

Abbreviations: PEG, polyethylene glycol; PMT1, microtablet-incorporating coarse phenylephrine powders; PMT2, microtablet-incorporating phenylephrine dry nanosuspension; PVPP, polyvinylpyrrolidone; CMS Na, sodium starch glycolate; DNPE, phenylephrine dry nanosuspension.

Table 2 Preparation process and apparent solubility of nanosuspensions

	Media milling (minutes)	Apparent solubility after 72 hours (mg/mL)
NPE1	0	10.37
	5	12.54
	10	14.12^a
	15	13.91
	20	13.44
NPE2	10^b	17.18

Notes:

a Selected for further studies;

b Homogenized for 30 minutes following the milling process.

Abbreviations: NPE1, phenylephrine nanosuspension prepared by milling in a mannitol aqueous solution; NPE2, phenylephrine nanosuspension prepared by high pressure homogenization of NPE1.

Table 3 Particle size, polydispersity index (PDI) and zeta-potential of coarse powder or nanosuspensions of phenylephrine

	Particle size (nm)	PDI	Zeta-potential (mV)
Coarse	>1000
NPE1	832.4	0.294	−26.0
NPE2	500.3	0.333	−16.7
DNPE	216.8	0.416	−15.1

Abbreviations: NPE1, phenylephrine nanosuspension prepared by milling in a mannitol aqueous solution; NPE2, phenylephrine nanosuspension prepared by high pressure homogenization of NPE1; DNPE, phenylephrine dry nanosuspension.

Figure 2 Transmucosal flux of phenylephrine through the porcine buccal mucosa versus the concentration of phenylephrine solution.

Figure 3 Permeation of phenylephrine through the porcine buccal mucosa, as a function of time. Results are shown for phenylephrine solution (9.91 mg/mL), phenylephrine-hydroxypropyl-β-cyclodextrin complex (PE-HPβCD) and phenylephrine nanosuspensions. In all cases, the dose that was applied was 2 mg of phenylephrine.

Abbreviations: NPE1, nanosuspension prepared by milling in a mannitol aqueous solution; NPE2, nanosuspension prepared by high pressure homogenization of NPE1; DNPE, phenylephrine dry nanosuspension.

Figure 4 Permeation of phenylephrine through the porcine buccal mucosa, as a function of time. Results are shown for the buccal patch containing coarse phenylephrine powder in the microtablet (PMT1), and the buccal patch containing phenylephrine dry nanosuspension in the microtablet (PMT2).