Study Of A Timolol Maleate Gel Used For Infantile Hemangiomas Treatment

Objectives: Combined with the clinician and patient's reflection on the treatment of infantile hemangiomas,we often use an external application of timolol maleate eye drops,which is off-label drug use.Based on the characteristics of infants hemangiomas,the physical and chemical properties of timolol maleate,and the uniqueness of infant skin,a new preparation named timolol maleate gel was developed,to improve inconvenient and poor effect of eye drops,to meet the actual clinical needs.Methods: Based on the ChP and related literatures,an in vitro analysis method for timolol maleate gel was established by ultraviolet spectrophotometry(UV)and high performance liquid chromatography(HPLC);Through formula single factor investigation and orthogonal design experiment,to find stable and safe gel excipients,to determine the best prescription and process;The transdermal diffusion tester was used to simulate the transdermal release of drugs,to investigate the permeability difference of TM gel in different animal skins,and to analyze the percutaneous kinetics of drugs;Evaluate the quality of TM gel from character,identification,inspection and content determination;The stability of TM gel was investigated through influencing factor experiments,accelerated experiments and long-term experiments.Results: Establishing an in vitro analysis method for timolol maleate gel by UV and HPLC,with excellent specificity,recovery,precision;Through formula single factor investigation and orthogonal design experiment,the best formulation of the gel(10g)was selected: timolol maleate 68.34 mg,carbopol 940 0.10 g,glycerol 0.50 g,propylene glycol1.00 g,phenethyl ester 0.01 g,triethanolamine 0.135 g,appropriate amount of water;The transdermal permeability of TM gel in three commonly used skin barrier materials of rats,nude mice and Bama mini-pigs varies among species: SD rats have the largest skin permeability,followed by nude mice,and pig skins have the lowest,both of them have some drugs to resist the barrier effect of the stratum corneum and enter the lesion site to play a medicinal effect;The in vitro release of the preparation in the skin of the three animals conforms to the zero-order kinetic process,that is,the drug release in the gel is mainly diffusion-based;The quality of TM gel is good and meets the requirements of thegelatin quality standards in the ChP;The results of the stability investigation showed that the stability of the TM gel was good in 6 months of acceleration and 9 months of long-term.Conclusions: The stable,safe and effective TM gel was successfully prepared.The prescription is reasonable,the process is simple,the stability is good,and it meets the quality requirements of the gel in ChP.It is suitable for infant hemangiomas and solves the disadvantages of inconvenient and poor effect of eye drops,meets the actual clinical needs effectively.