Entrapment of andrographolide in cross-linked alginate pellets: I. Formulation and evaluation of associated release kinetics.

Andrographolide, the 'King of bitters' requires high doses in the form of an extract (33.3%w/w) to be used as a hepatoprotectant. Since a large dose of this herb is known to cause gastric distress, vomiting, loss of appetite and nausea on regurgitation, it was thought of to convert the drug itself into a bitterless micropellet. The technique of ionotropic gelation of sodium alginate with calcium ions with subsequent drug entrapment was employed. The optimization of process parameters like the bore diameter of the needle, % concentration of sodium alginate, method of drying, drying time and temperature, time of contact of the micropellets in calcium chloride solution and concentration of calcium chloride to be used for the gelation were undertaken. The micropellets were finally prepared by adding 2.5%w/v of sodium alginate into a 2%w/v solution of calcium chloride solution using 20-guage flat tip needle and dried using a hot air oven at 60(o)C for 6 hrs. The so formed pellets were completely bitterless and released the andrographolide preferably away from the stomach. Pellets with varied drug: polymer ratio (1:2, 1:1 and 2:1) were prepared accordingly and analyzed for release kinetics. Release studies showed only about 15% release upto 4 hrs in pH 1.2 and pH 4.0 respectively and released the remaining in pH 7.4. The data obtained in the dissolution studies was fitted into various mathematic models defining kinetics of drug release like the zero-order rate equation, first-order rate equation, Hixson-crowell, 2/3rd rule, Korsemeyer-Peppas, Baker-lonsdale, Higuchi, Weibull, Ford and Hopfenberg Equation. The release kinetics of andrographolide from the alginate pellets was found to be best described by the korsemeyer-peppas equation which provided n values ranging from 1.0-1.47 with good linearity of the best-fit line (R(2)=0.9973). In conclusion, andrographolide can be easily converted to bitterless multiple unit dose oral delivery systems with good entrapment efficiency and a maximum release of 86% by utilizing the technique of ionotropic gelation.

Entrapment of andrographolide in cross-linked alginate pellets: II. Physicochemical characterization to study the pelletization of andrographolide.

This paper deals with the characterization of pellets containing andrographolide in two parts. The first part deals with characterization of the pellets to ascertain the identity and integrity of andrographolide. Part two involves characterization of the pellets containing Andrographis paniculata extract (33.3%) prepared in the paper I for their micromeritic properties like Particle size, Particle size distribution, Sphericity measurements like Shape ratio and Aspect ratio, Tapped density, Compressibility index, Hausner's ratio and Angle of repose. In addition, our aim was also to derive information about the mechanism of gelation with entrapment of andrographolide to supplement results obtained about the release mechanisms deduced in paper I. Since this work requires use of techniques like FTIR, FTRaman, MTDSC and XRPD, it was necessary to prepare alginate micropellets using pure andrographolide (99.89%) rather than the multicomponent extract using the same procedure discussed in paper I. The integrity of the drug was maintained in the cross-linked micropellets as was seen in the MTDSC and FTIR spectra supported by the FTRaman spectra. The depolymerisation transitions, the reversing and non-reversing heat flow signals were determined using the MTDSC and interpreted to study the mechanism of pelletization. The MTDSC profiles also confirmed the integrity of the drug by exhibiting a sharp endotherm at 232(o)c that is the melting point of andrographolide. The XRPD spectrum of the micropellets ascertained that the crystallinity of andrographolide was maintained. The relationship of the nature of the drug present in the micropellets related to release mechanisms is discussed. In conclusion, it can be said that andrographolide can be successfully incorporated into cross-linked micropellets of alginate without affecting its integrity or nature to deliver it as a bitterless monoherbal preparation.