1. FORMULATION AND IN VITRO EVALUATION OF ATORVASTATIN SOLID DISPERSION
MANDAL SANTA, DEY SANJAY, GHOSH AMITAVA
BENGAL COLLEGE OF PHARMACEUTICAL SCIENCES AND RESEARCH
B.R.B.SARANI, BIDHANNAGAR, DURGAPUR , WEST BENGAL, INDIA
INTRODUCTION
Up to 40% of new chemical entities discovered by the pharmaceutical industry today are poorly soluble or lipophilic compounds. The solubility issues complicating the delivery of these new drugs also affect the delivery of many existing drugs. Oral bioavailability of a drug depends on its solubility and/or dissolution rate, & dissolution may be the rate determining step for the onset of therapeutic activity. Therefore, efforts to increase drug dissolution of drug are after needed. Methods available to improve dissolution include salt formation, micronization & addition of solvent or surface active agent. Atorvastatin as a synthetic lipid-lowering agent, is an inhibitor of HMG- CoA reductase which catalyzes the conversion of HMG CoA to mevalonate, an early rate limiting step in cholesterol biosynthesis. It is insoluble in aqueous solution of pH 4 and below. it is very slightly soluble in water and pH 7.4 phosphate buffer. The intestinal permeability of atorvastatin is high. The absolute bioavailability of atorvastatin was found 12% after 40 mg oral dose. In this paper, the solid dispersions of valdecoxib with PEG 4000 were prepared by the melting method, and the same was characterized by dissolution, FTIR, XRD, and DSC.
MATERIALS: Atorvastatin (ATV) was obtained as gift sample from Cipla Ltd..Mumbai. PEG 4000 was purchased from Merck, Mumbai, India.
METHODS
Determination of solubility of atrovastatin in different media.
Preparation of physical mixture and solid dispersion using
PEG 4000 (1:1, 1:2, and 1:3)
Physicochemical characterization of physical mixture and
solid dispersion
FTIR
DSC
XRD
In vitro dissolution study of the pure drug, physical
mixture, and solid dispersion,
ATV
ATV
PEG4000 PM PM SE SE
Fig.1: IR spectrum
Fig.2: DSC thermogram
Table 1:Solubility Studies of Pure Drug & Solid Dispersion in Different Media
RESULT AND DISCUSSION
All the test samples showed an increase in drug solubility as the amount of carrier increased.
Maximum solubility was observed in solvent evaporation method (1:3 Drug:PEG4000), when compared with that of pure drug (Table 1).
These observations indicated the compatibility of PEG-4000 with ATV (FIG. 1).
(Fig. 2).
XRD spectra revealed that the intensity of the peak was decreased in SE as compared to PM which might be due to conversion of crystalline from to amorphous from of drug (Fig. 3).
The dissolution rate was significantly increased when the ATV: PEG 4000 ratio was at 1:3 (Fig. 4).
The mean percentage of drugs for physical mixture after 60 minutes was , and % for 1:1, 1:2, 1:3 respectively.
But in the solvent evaporation method half fold increase in release rate was observed as , and % respectively. This may be due to impact of complexation and bond formation. This may lead improved solubility by reducing particle size.
ATV
State
Formulation
Solubility (µg/ml)
Water
0.1(M)HCl
Pure
Atrovastatin
27.04±0.56
57.06±0.67
Physical mixture
1:1
35.59±1.12
63.78±1.19
1:2
46.87±1.24
72.76±1.21
1:3
57.59±1.35
81.89±2.35
Solvent evaporation
36.22±1.05
65.12±1.13
48.86±1.87
73.52±1.15
58.92±1.46
83.42±1.76 PM SE
Fig.3: XRD diffractrometry
Fig. 4: In vitro release profile
CONCLUSION
The solubility and dissolution rate of atorvastatin can be enhanced by the use of SDs of atorvastatin with PEG From FTIR spectroscopy, it was concluded that there was no well defined interaction between atorvastatin and PEG 4000, since no new peaks or shift of peaks could be observed. The absence of an endothermic peak of atorvastatin in the DSC thermograms of SDs with PEG 4000 showed the conversion of atorvastatin from crystalline to amorphous state. In addition, XRD and SEM studies supported the conclusion drawn from the DSC study. It can be concluded that the preparation SDs of atorvastatin with PEG 4000 provides a promising way to enhance its solubility and dissolution rate.
REFERENCES
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