TIME hours

Figure 5 Release of BPO dispersed in vehicle (■) abd BPO entrapped in porous microspheres and dispersed in vehicle (•). Results are the average of two determinations. Formulations applied to silastic membrane. Receiving fluid 1:1 mixture of water and acetone. (From Ref.

Cumulative 14-day irritancy scores in human volunteers are shown in Figure 6 and Table 1. In this study involving 29 patients, total irritaancy of four commercial products, three containing free BPO and one containing entrapped BPO at the BPO concentrations shown, were compared. Clearly, the entrapped BPO product is significantly less irritating. A 12-week human trial, comparing the efficacy of entrapped BPO formulations at various concentrations, a placebo formulation and a free BPO formulation has also been carried out. The total reduction of inflammatory lesions shown in Figure 7 and the total reduction of noninflammatory lesions shown in Figure 8 clearly shows that the entrapped BPO is as efficacious as the free BPO. These results support evidence also obtained independently, that most, if not all, BPO entrapped in the porous microspheres is released.

Retinoic Acid

All trans-RA is a highly effective topical treatment for acne vulgaris. However, cutaneous irritation reduces patient compliance, and thus clinical effectiveness. A gel formulation with 0.1% RA entrapped in a porous microsphere has been developed and a single-center, double-blind, positive-controlled, randomized Phase I study carried out. The formulation with entrapped RA was designated as 0.1% TMG (tretinoin microsphere gel), and the one with free RA was designated 0.1% RA cream. Either study formulation was assigned to be applied to the right side of a subject's face on a randomized basis, the alternate formula-

Figure 6 Fourteen-day cumulative irritancy test on BPO formulations in human volunteers comparing three commercial products containing BPO dispersed in a vehicle and one commercial formulation containing BPO entrapped in porous microspheres at BPO concentrations shown.

tion to the left side of the face. The dose for each formulation was 0.1 g, which was applied to the cheek areas once daily for up to 14 days. The subjects were evaluated daily by an expert grader for dryness and erythema. Results of subjects' self-assessment are shown in Table 2 and in Figure 9. Clearly, a formulation with RA entrapped in porous microspheres resulted in a statistically significant preference for the TMG formulation,

Table 1 14-day Cumulative Irritancy in Human Volunteers

Formulation

% Total subjects with postive response

Cumulative response index*

2.5% BPO

Commercial product

36

1.04 (1)

Entrapped BPO

12

0.24 (2)

Vehicle

0

0.0 (3)

10% BPO

Commercial product

52

2.59 (4)

Entrapped BPO

24

1.64 (5)

Vehicle

0

0.0 (6)

* Duncan's Multiple Range tests showed significant difference (p < 0.05) between (1) and (2), (1) and (3), (4) and (6), (5) and (6), but no significant difference (p > 0.05) between (2) and (3). Source: Ref. 14.

* Duncan's Multiple Range tests showed significant difference (p < 0.05) between (1) and (2), (1) and (3), (4) and (6), (5) and (6), but no significant difference (p > 0.05) between (2) and (3). Source: Ref. 14.

Figure 7 Percent reduction in total inflammatory lesions (papules/pustules) in human volunteers at 2, 4, 8, and 12 weeks, using the formulations shown.

Figure 8 Percent reduction in total noninflammatory lesions (open and closed comedones) in human volunteers at 2, 4, 8, and 12 weeks, using the formulations shown.

Figure 8 Percent reduction in total noninflammatory lesions (open and closed comedones) in human volunteers at 2, 4, 8, and 12 weeks, using the formulations shown.

Table 2 Subject Self-Assessment

Number who prefer 23 2

Preference scoref 1.88 0.10 0.0002

f Preference score perceived as less burning and/or stinging graded on a scale from 0 (no difference) to 4 (maximal difference).

Figure 9 Daily self-assessment of preference for mildness. Single-center, double-blind, randomized, half-face study comprising 25 adult Caucasian women selected for having sensitive skin. 0.1% TMG is retinoic acid entrapped in porous microspheres and 0.1% RA cream in a commercial formulation. 0.1% TMG and 0.1% RA cream applied to corresponding side of subject's face, once a day for up to 14 days by a blinded technician.

DAYS OF TREATMENT

Figure 9 Daily self-assessment of preference for mildness. Single-center, double-blind, randomized, half-face study comprising 25 adult Caucasian women selected for having sensitive skin. 0.1% TMG is retinoic acid entrapped in porous microspheres and 0.1% RA cream in a commercial formulation. 0.1% TMG and 0.1% RA cream applied to corresponding side of subject's face, once a day for up to 14 days by a blinded technician.

which was perceived as causing less burning and stinging. In an independent, controlled multicenter trial, this TMG formulation has also proven effective for the treatment of acne and is now commercially available.

Beauty for Newbies

Beauty for Newbies

Do you feel like an ugly duckling sometimes? Doesn't it seem like everyone else seems to know the best ways to present themselves, from their hair, to their skin, to their makeup?

Get My Free Ebook


Post a comment