Efficacy and tolerability of a double-conjugated retinoid cream vs 1.0% retinol cream or 0.025% tretinoin cream in subjects with mild to severe photoaging.

BACKGROUND: Topical retinoids are used to treat the visible signs of photoaging. While efficacious, they are irritating. OBJECTIVE: Evaluate the effectiveness and tolerability of a double-conjugate retinoid cream (AlphaRet Overnight Cream; AHA-Ret) in improving visible signs of photoaging vs 1.0% retinol or 0.025% tretinoin. METHODS: A 12-week, split-face, randomized trial was conducted in 48 female subjects, aged 30-65 years with mild to severe photodamage. AHA-Ret was applied to one side of the face and either retinol (n=24) or tretinoin (n=24) to the other side (PM). Expert blinded evaluation of images and Nova measurements occurred at 4, 8, and 12 weeks. Tolerability was assessed throughout the study. RESULTS: Forty-seven subjects completed the study. AHA-Ret demonstrated significant reductions in average severity from baseline: Fine Lines/Wrinkles (P<.001; all time points); Erythema (P=.004, P<.0001; 8 and 12 weeks, respectively); Dyschromia (P<.0001; all time points); Skin Tone (P<.0001; all time points), and Pore Size (P=.035, P<.0001; 8 and 12 weeks, respectively). AHA-Ret induced less Erythema vs retinol at 8 (P=.008) and 12 (P<.02) weeks. AHA-Ret was noninferior to prescription tretinoin in all categories at 4 and 8 weeks, and for Fine Lines/Wrinkles, Erythema, Dyschromia, and Skin Tone at 12 weeks. Improvements in Hydration occurred at every time point with AHA-Ret only (P<.04, P<.03, P<.01). Less irritation was reported with AHA-Ret vs retinol or tretinoin. CONCLUSIONS: Treatment with a double-conjugate retinoid cream demonstrated early reductions in photodamage and improvements in Hydration. AHA-Ret induced less Erythema vs retinol and was more tolerable vs retinol and tretinoin.

Rheological evaluation of the physical properties of hyaluronic acid dermal fillers.

BACKGROUND: Hyaluronic acid (HA) gels are commonly injected into the skin to lift rhytides and to improve facial appearance. The different processes used in their manufacture and formulation yield products with unique physical characteristics that play an important role in predicting their clinical performance. OBJECTIVE: The following rheologic evaluation was performed to objectively measure the physical characteristics of HA dermal filler products derived from similar bacterial sources and containing the same butanediol diglycidyl ether cross-linker, but formulated using different manufacturing techniques. The objective of this study was to evaluate the physical characteristics of two distinct families of HA products, thereby providing clinicians with a greater understanding of these products' attributes and the ability to optimize their use in the treatment of patients seeking facial rejuvenation. MATERIALS AND METHODS: The physical properties of commercially-available dermal fillers containing HA were evaluated using rheologic testing methods under clinically-relevant conditions. Additionally, light microscopy was used to assess the particulate nature of each product. RESULTS: The gels tested demonstrated a broad range of elasticity, firmness and viscosity. Light microscopy confirmed the particulate nature of each product and revealed HA particles of varying size and distribution. CONCLUSION: This rheologic evaluation demonstrates that differences exist among the HA products tested including gel elasticity, viscosity, and the range and distribution of gel particle sizes. Understanding the distinct physical characteristics of different HA dermal fillers and how these characteristics may predict their clinical behavior can assist clinicians in achieving the desired results in patients seeking facial rejuvenation.

The science and manufacturing behind botulinum neurotoxin type A-ABO in clinical use.

BACKGROUND: Since the first comprehensive description of the physiologic effects of botulism toxicity in the 1820s, specific formulations of botulinum neurotoxin type A (BoNT-A) have been developed. Now, a new botulinum neurotoxin type A formulation (BoNTA-ABO; Dysport [abobotulinumtoxinA]; Medicis Aesthetics, Scottsdale, AZ) has been made available in the United States and these same physiologic effects have become beneficial clinical targets. This formulation has been used successfully for nearly 20 years in Europe and other countries under the trade name Dysport (Clostridium botulinum type A toxin-hemagglutinin complex; Ipsen Biopharm, Wrexham, UK). BoNT-A injections are administered to achieve temporary local flaccid paralysis of targeted muscles. Injection of BoNT-A formulations for aesthetic purposes was by far the most common minimally-invasive (nonsurgical) cosmetic procedure performed in the United States in 2008. OBJECTIVE: The objective of this review is to describe the latest data regarding the mechanism of action of BoNTA-ABO, the potential roles of neurotoxin-associated proteins (NAP), the manufacturing standards for these biologic products, and the specific manufacturing process and characteristics of BoNTA-ABO. METHODS: A systematic search using the US National Library of Medicine PubMed database was performed and the relevant articles were reviewed. Direct input and data from the worldwide manufacturer of Dysport have been included. RESULTS: The four sequential steps in the mechanism of action of BoNTA-ABO are binding, internalization, translocation, and intracellular proteolysis of the target protein. Although all BoNT-A products must meet standards for quality, potency, and safety, they should not be considered equivalent formulations because they have different production strains of the bacterium C botulinum, as well as different isolation and manufacturing processes that result in unique product characteristics. The production steps for Dysport-including a unique proprietary purification process using column chromatography and a unique proprietary finishing process-result in consistent and unique product features. Studies confirm that Dysport has a high degree of long-term batch-to-batch consistency for a range of specified properties, including specific potency, protein composition, toxin complex charge-density properties, and endopeptidase activity. In the native, natural form, NAP protect the endogenous neurotoxin from degradation in the acidic environment of the stomach; in biologic formulations, they may have effects on the structural stability, binding, uptake, and transcytosis of BoNT-A products in other areas of the body. NAP are most likely to stabilize the neurotoxin in a vial of clinical product. CONCLUSIONS: A thorough understanding of the mechanism of action, product characteristics, and effects of NAP is important to ensure appropriate and safe clinical use of BoNT-A products. Now approved in the United States, Dysport is an important addition to the group of available BoNT-A formulations.

Key bioavailability features of a new extended-release formulation of minocycline hydrochloride tablets.

For a long time, minocycline has been recognized as highly efficacious for the treatment of acne vulgaris but with use-limiting acute vestibular adverse events (AVAEs). Based on the concept that lowered overall systemic exposure to minocycline should reduce unwanted side effects, a program was initiated to develop a modified-release formulation for clinical testing. An extended-release (ER) minocycline hydrochloride tablet formulation was developed that demonstrated delayed time of maximum concentration (tmax, 3 1/2 - 4 hours) compared with a nonmodified-release minocycline (tmax, 2 1/4 - 3 hours), and a lower maximum concentration of drug (cmax) in the blood (90%) compared with nonmodified-release formulations. At steady state (day 6), the ER-minocycline formulation had a 0- to 24-hour area under the curve (AUC(0-24)) and cmax of 33.32 microg x h/mL and 2.63 microg/mL, respectively, compared with 46.35 micro x h/mL and 2.92 microg/mL, respectively, for the nonmodified-release minocycline. These studies demonstrated that the new ER-minocycline hydrochloride formulation is not bioequivalent to the immediate-release (IR) minocycline hydrochloride formulation currently on the market. The favorable pharmacokinetic profile of ER minocycline also was not affected by concomitantly ingested food, including dairy products.