Development& Characterization Of Calcitriol Loaded In-Situ Gel For Enhancing Orthodontic Tooth Movement

Abstract

Introduction: Orthodontics is defined as the dental specialty that deals with tooth abnormalities and how to fix them (employing forces) e.g., braces. In orthodontic treatment, there is an application of force on the teeth to align them properly. Treatment time for comprehensive orthodontic treatment varies widely, but the best evidence currently available, based on predictive studies conducted in university settings, suggests that successful treatment takes around two years. According to the 2015 AAO Economics of Orthodontics Survey, in 2014, an average orthodontist handled 125 adult patients, rising from 41 adult patients in 1989.For enhancing orthodontic tooth movement there is various treatment in India but all are invasive. So, there is an urgent need to develop a novel formulation to enhance orthodontic tooth movement. Therefore, for enhancing orthodontic tooth movement, we have developed an in-situ gel that is non-invasive. The in-situ gel was prepared by using the cold process method. The choice of drug was Calcitriol. The selected Calcitriol is a synthetic Vitamin D analog approved by US FDA in 1986. Calcitriol is a white, crystalline compound. It has a calculated molecular weight of 416.6. It is freely soluble in organic solvents but relatively insoluble in water. Rocaltrol (Brand name of calcitriol) comes as capsules that contain 0.25mcg or 0.5mcg of calcitriol, as well as an oral solution with 1mcg/ml of calcitriol. Materials and method: In the current work, Calcitriol loaded in-situ gel was developed and prepared by cold process method. In this study, Poloxamer 407 and calcitriol was used as the main component. After preparation of in-situ gel they are further evaluated for various evaluation parameters like pH, drug content, Fourier transform infrared spectroscopy, gelation time and gelation temperature, in-vitro drug release, ex-vivo drug permeation, gel strength, stability studies. Results and Discussion: Calcitriol was authenticated by FT-IR, melting point and UPLC which confirmed that the procured drug was calcitriol and it was pure and free from any impurity. The melting point of the drug was found to be 113.5℃. From the various literature review, it was concluded that Calcitriol showed a major peak at 265nm. From UPLC analysis the linear regression equation was found to be y = 9306x + 162.5 and coefficient of correlation value (R2) 0.999. The limit of detection (LOD) and limit of quantification (LOQ) was found to be 0.029µg/ml and 0.087µg/ml, respectively which indicate the sensitivity of the method. Various other parameters such as accuracy, precision, and robustness were within the limits of ICHQ2 (R1) guidelines. In the formulation of temperature-sensitive in-situ gel Poloxamer 407 was used in different concentrations. Based on gelation time and temperature the formulation containing 25% of poloxamer was selected for the in-vitro and in-vivo studies. The formulated in-situ gel was then evaluated and found that the developed formulation was clear and transparent, had a pH of 7.00, and the formulation was converted into gel at 37℃ within 4 seconds. The in-situ gel was also evaluated for the syringiablity and spreadability and found that it was easily passable from the syringe and could be easily spread within the area of 11.704 cm2. The prepared formulation was also evaluated for in vitro drug release and ex-vivo permeation study at predetermined rate (15 sec., 30sec, 45sec., 60sec., 90sec., 120sec.,) and was found that the formulation release 98.72% of drug at 120 sec. during in vitro drug release study and 71.2% of drug at 120 sec. during ex vivo permeation study.The in-situ gel was then evaluated for skin deposition which was 28.92%. The prepared in-situ gel was stable for three months at room temperature based on physical appearance, pH, clarity, gelation time, and temperature. Owing to the gelation capacity of the polymer the prepared formulation was planned to deliver at the local site (gums) in the form of liquid drops which were then converted into gel within seconds due to temperature changes. As a result, it attains a good therapeutic effect in orthodontic treatment with reduced systemic effects.