I've been preparing an oral dispersible film of Meclizine HCL (25 mg) that has to be solubilized in water. Unfortunately, it is almost insoluble in water (0.1 mg/ml). I tried using complexation method with cyclodextrins, solid dispersion method taking PEG 4000 as a carrier, used sodium citrate to shift the pH to an upper range so that drug ionization takes place aiding in enhanced solubility; however, the result has not been as promising as I would have liked. I would be grateful to get your inputs. Thank you.
Sandeep, sodium citrate will generate a basic environment and tend to *depress* the solubility of the drug (any hydrochloride which reacts will leave the insoluble free base)? You want to *ionize* it instead -- so try adding citric acid to your formulation. This will generate a local acid environment which may assist the drug movement (by diffusion) into your dissolution medium. (Personally, I prefer the taste of malic acid to that of citric!) Or, formulate your oral film so as to be substantially soluble -- the drug will be released; whether or not it remains so will depend on its solubility vs. its instantaneous concentration, and presence of suspended solids on which it may precipitate.
Studies on the Preparation, Characterization, and Solubility of 2-HP-β-Cyclodextrin-Meclizine HCl Inclusion Complexes
SJ George and DT Vasudevan
Abstract
Meclizine HCl is a poorly water-soluble drug having a very slow-onset of action. The effect of 2-hydroxypropyl-β-cyclodextrins and β-cyclodextrins on its aqueous solubility and dissolution rate was investigated. The phase solubility profile indicated that the solubility of Meclizine HCl was significantly increased in the presence of both 2-hydroxypropyl-β-cyclodextrin and β- cyclodextrin; an extend of increase being more for 2-hydroxypropyl-β-cyclodextrin. It was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. The complexes formed were quite stable. The solid complexes prepared by physical mixtures, kneading methods, and co-precipitation methods were characterized using differential scanning calorimetry and FTIR. An in vitro study showed that the solubility and dissolution rate of Meclizine HCl were significantly improved by complexation with 2-hydroxypropyl-β-cyclodextrin. Tablet formulation using 1:1 kneading complex of Meclizine HCl and 2-hydroxypropyl-β-cyclodextrin with drug equivalent to 25 mg was prepared by a direct compression method. A dissolution study of prepared tablets was performed in 0.5% SLS in water (pH 7.0). Almost 96% drug was released from the formulation at the end of 30min. A comparison study of prepared tablets was done with marketed a Meclizine HCl 25 mg conventional tablet. From the results of dissolution study, it was found that the prepared formulation was showing better release, which was statistically significant P < 0.01 than a marketed tablet (paired t-test). Only 54% drug release was observed from the marketed tablet at the end of 30 min. Hence this study concludes that the solubility enhancement of Meclizine HCl could be successfully achieved using the inclusion complexation technique.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573373/
You can make trial by using surfactant micellization. Use some type of surfactants like Spans or Tweens to get your drug solubilized.
Formulation Development and Characterization of Meclizine Hydrochloride Sublimated Fast Dissolving Tablets
Sateesh Kumar Vemula1,2 and Mohan Vangala2
Abstract
The intention of present research is to formulate and develop the meclizine hydrochloride fast dissolving tablets using sublimation method to enhance the dissolution rate. In this study an attempt was made to fasten the drug release from the oral tablets by incorporating the superdisintegrants and camphor as sublimating agent. The prepared fast dissolving tablets were subjected to precompression properties and characterized for hardness, weight variation, friability, wetting time, water absorption ratio, and disintegration time. From in vitro release studies, the formulation F9 exhibited fast release profile of about 98.61% in 30 min, and disintegration time 47 sec when compared with other formulations. The percent drug release in 30 min () and initial dissolution rate for formulation F9 was 98.61 ± 0.25%, 3.29%/min. These were very much higher compared to marketed tablets (65.43 ± 0.57%, 2.18%/min). The dissolution efficiency was found to be 63.37 and it is increased by 1.4-fold with F9 FDT tablets compared to marketed tablets. Differential scanning calorimetry and Fourier transform infrared spectroscopy studies revealed that there was no possibility of interactions. Thus the development of meclizine hydrochloride fast dissolving tablets by sublimation method is a suitable approach to improve the dissolution rate.
https://www.hindawi.com/journals/isrn/2014/281376/
In place of trying other techniques like solid dispersion, complexation, change of pH, micronization. You may select either self emulsifying drug delivery system or microemulsion by using various oils, surfactants and cosurfactants.
- Badges
- Science topic
- Similar topics
- Mathematics