**8. Challenges in developing topical medications for psoriasis**

The unique nature of drug delivery across the skin also presents with several unique challenges in development of topical products, such as:


In addition to these general challenges in topical formulation development, there are several challenges specific to psoriasis and the development of antipsoriatic topical products, such as:


clobetasol propionate (0.05% spray) twice daily for up to four weeks. At the end of four weeks, if the patient's overall disease severity was assessed as clear, almost clear, mild or moderate, the patients were treated with calcitriol (3 μg/g ointment) twice daily for an additional eight weeks (upto week 12) or unless the patient's disease was assessed as severe or returned to the baseline score, at which time the treatment was discontinued. Patients were evaluated at baseline and at 2, 4, 8 and 12 weeks. In 84% of the patients who completed the 12 week study, this treatment resulted in at least one grade improvement in disease severity and hence was considered successful as per predefined criteria. There was a significant decrease in the percent body surface area affected, from 7.1% at baseline to 3.9% at week 12. The sequential treatment regimen was also well tolerated with no unexpected adverse events. Most reported adverse events and skin irritations were mild in severity

The unique nature of drug delivery across the skin also presents with several unique

1. Optimization of both drug property and formulation composition to enhance the rate

2. Reduced drug concentration and increase in data variability due to presystemic

3. Switch of topical formulations during clinical development that can be very challenging, hence only minimal formulation changes can be usually made during

4. No control on deep tissue penetration through formulation approaches, which is

5. Lack of confidence in dose projection due to difficulty in establishing robust skin

6. High variability in *in vitro* and *in vivo* skin permeability remains a major obstacle in

7. Guidances from regulatory agencies often call for clinical comparisons of innovative drugs with approved active comparators, thus increasing the challenges for

8. Regulatory standards call for demonstration of benefit for each component within a fixed dose combination product, the so-called "Combination Rule", another challenge in

In addition to these general challenges in topical formulation development, there are several challenges specific to psoriasis and the development of antipsoriatic topical

1. Psoriatic lesions can have both thickened and markedly thinned epidermis, this heterogeneity in the skin morphology can increase the variability in drug permeation and systemic absorption, thus increasing challenges in formulation development; 2. A significant number of psoriasis patients feel that the current therapies are either not sufficiently efficacious or aggressive. Hence, a primary challenge is to develop new

**8. Challenges in developing topical medications for psoriasis** 

and extent of drug diffusion through the stratum corneum;

primarily influenced by protein binding and dermal blood flow;

challenges in development of topical products, such as:

pharmacokinetic-pharmacodynamic relationship;

using these tools in formulation development;

development and licensure of novel products;

development of a combination product.

(Brodell et. at., 2011).

metabolism in the skin;

development;

products, such as:

therapies which can be once daily application and show quick response, such as within the first four weeks of treatment;

