EMPEZAR A BORDAR 51 - Manual de instrucciones

• IR studies

Drug-polymer interaction study was carried out for physical mixture of pure drug(Flurbiprofen) and HPMC.The results rule out the incompatibility between drug and polymer ( Fig 5.13)

• Thickness

The thickness of the CAP coating was measured by using screw gauge. The values ranged from 0.053-0.065 mm. (Table 5.10)

• In-vitro release studies

The dissolution studies, depicits the enteric coat of the cellulose acetate phthalate was intact for nearly two hours in pH 1.2, but dissolved in intestinal pH, leaving the soluble cap of capsule, which also dissolved in pH 7.4 phosphate buffer. The exposed HPMC polymer plug which absorbed the surrounding fluid, star swelling and release the drug through the swollen matrix. After complete wetting of the plug, it formed a soft mass, which was then easily ejected out of the capsule body; releasing the eudragit microspheres into simulated colonic fluid (pH 6.8 phosphate buffer).

Department of Pharmaceutic Department of Pharmaceutic Department of Pharmaceutic

Department of Pharmaceutics, Bharathi College of Phs, Bharathi College of Phs, Bharathi College of Phs, Bharathi College of Pharmacy armacy armacy armacy 69696969 In all the formulations, there was absolutely no drug release in pH 1.2, thus indicating the efficiency of 5% CAP for enteric coating. Very slight release was observed in pH 7.4 phosphate buffer.

The F5, F6, F7 formulation at the end of 15th hrs shows the drug release of 75.96 %, 72.01 % and 59.92 % respectively. As the concentration of polymer increases the drug release decreases. (Tables 5.12 to 5.14 and Fig 5.14)

The r2 value in higuchi plot confirms the drug release by Higuchi diffusion mechanism. The formulations were subjected to peppas plots by taking log cum % drug released versus log time. The plots are found fairly linear and the ‘r2’ values are near to 1 and also slope value was calculated (n value) which was in ranges of 2.459 to 2.724, indicating the drug was released by Super Case II transport diffusion mechanism. (Table 5.15 and Figs 5.15 to 5.18)

Department of Pharmaceutics, Department of Pharmaceutics, Department of Pharmaceutics,

Department of Pharmaceutics, Bharathi College of Pharmacy. Bharathi College of Pharmacy. Bharathi College of Pharmacy. Bharathi College of Pharmacy. 70707070 The results obtained from the study of “Design and evaluation of chronotherapeutic drug delivery system of flurbiprofen ” provide the following conclusion

• The particle size increased significantly as the amount of polymer increased. • The flow properties of all the prepared microspheres were good as indicated by

low angle of repose (θ < 40º).The good flow properties suggested that the microspheres produced were non-aggregated.

• As the entrapment efficiency was good in all the cases, suggest that optimized parameters were used in the method of preparations.

• The In-vitro drug release of microspheres exhibits two type release pattern for all microspheres with initial burst release effect, which may be attributed to the drug loaded onto the surface of the particles.

• On the basis of, particle size, drug content, Scanning Electron Microscopy, IR- study, in-vitro release studies and its kinetic data, F3 was selected as an optimized formulation for designing pulsatile device.

• The 1:2 ratio of Eudragit L-100 and S-100 are suitable for preparation of microspheres for colonic targeting.

• The solubility studies of formaldehyde treated empty gelatine capsule bodies, signifies that they are intact for 24 hrs, and hence suitable for colon targeting. • Hence, finally it was concluded that the prepared pulsatile drug delivery system

can be considered as one of the promising formulation technique for preparing colon specific drug delivery systems and hence in chronotherapeutic management of arthritis.

Department of Pharmaceutics, Department of Pharmaceutics, Department of Pharmaceutics,

Department of Pharmaceutics, Bharathi College of Pharmacy. Bharathi College of Pharmacy. Bharathi College of Pharmacy. 71Bharathi College of Pharmacy. 717171 Over the past two decades there has been a growing appreciation on the importance of circadian rhythms on GIT physiology and on disease states, together with the realization of the significance of time-of-day of the administration on resultant pharmacodynamics and pharmacokinetics parameters.

The colon is a site where both local and systemic delivery of drug can take place. By targeting the drug to the colon the efficacy of the drug will be improved. In the present study, by keeping the objective of treating rheumatoid arthritis, an attempt was made to design and prepare chronotherapeutic, colon specific drug delivery system in order to target the drug to the colon.

Flurbiprofen microspheres were prepared using Eudragit L/S 100 in ratio 1:2 by emulsion solvent evaporation method. Four formulations (F1 to F4) were prepared by varying the ratio of the drug and polymer. IR-study reveals there is not significant interaction between drug and polymers. The prepared formulations were subjected to various evaluation parameters like particle size, flow properties, percentage yield, drug content, scanning electron microscopy and in-vitro drug release studies. From the results, the formulation F3 emerges as the optimum formulation to design time and pH dependent, pulsatile drug delivery system.

In the next step, the capsule bodies were made insoluble by formaldehyde treatment and these were subjected to various physical and chemical test such as dimension measurement, solubility studies and qualitative for free formaldehyde.

Department of Pharmaceutics, Department of Pharmaceutics, Department of Pharmaceutics,

Department of Pharmaceutics, Bharathi College of Pharmacy. Bharathi College of Pharmacy. Bharathi College of Pharmacy. 72Bharathi College of Pharmacy. 727272 The microspheres equivalent to 150 mg of drug was filled in to the formaldehyde treated capsule bodies and plugged with HPMC at different concentration (20, 30 and 40 mg). The joint of the capsule body and cap was sealed with small amount of 5 % ethycellulose ethanolic solution. Then these filled capsules were completely coated with 5 % cellulose acetate phthalate solution. These pulsatile formulations were subjected to various tests such as thickness of CAP coating, weight variation and in vitro release studies.

From the in vitro release studies of chrontherapeutic device, it was observed that with all the formulations, there was absolutely no drug release in simulated gastric fluid (acidic pH 1.2) for 2 hrs. Negligible amount of drug release was observed in simulated intestinal fluid (pH 7.4 phosphate buffer), where the dissolution were carried out for 3 hrs. At the end of 15 hrs the cumulative drug release for F5, F6 and F7 formulations was 75.96, 72.01 and 59.92 respectively.

The result obtained promises the development of chronotherapeutic system for time and pH dependant drug release for the treatement of rheumatoid arthritis. Further work is to establish the therapeutic utility of this system by pharmacokinetics and pharmacodynamic studies on human beings.

Department Department Department

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Department of Pharmaceutics, Bhara Department of Pharmaceutics, Bhara Department of Pharmaceutics, Bhara

Department of Pharmaceutics, Bharathi College of Pharmacy thi College of Pharmacy thi College of Pharmacy thi College of Pharmacy 80808080

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