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Abstract
Cyclodextrins have received much attention in the pharmaceutical field during the past two decades, due to their ability to form inclusion complexes and consequently change the physicochemical parameters, such as stability, solubility, dissolution rate and organoleptic properties, of many drugs resulting in development of more convenient dosage forms and better patient compliance. The increased availability and continuous decline in Cyclodextrin prices has broadened the aspects of Cyclodextrin use in the pharmaceutical field.
The aim of this work was to use and investigate the potential of different cyclodextrins, as multifunctional excipients, in solving some problems that face the formulators during dosage form design, using simple and available techniques.
This work was divided into two chapters:
Chapter One: Preparation and Evaluation of Fast Release Nimesulide-Cyclodextrin Binary Systems.
Different Nimesulide-β-CD binary systems in the molar ratio of 1:1 were prepared using simple physical mixing, sintering, cogrinding and wet granulation techniques. Wet granulation was performed using alcohol 50%, water at ambient temperature and hot water at 90°C as solvents. Different Nimesulide-β-CD derivatives (RM β-CD, HP β-CD and SBE β-CD) binary systems, in 1:1 M ratio, were also prepared by wet granulation using water at ambient temperature as the solvent. The prepared binary mixtures were characterized using DSC and FT-IR spectroscopy. The effect of CD type and preparation technique on enhancement of Nimesulide dissolution rate was studied. The binary systems were then subjected to an accelerated stability study, by storage at 40°C and 75% RH for three months.
Results of this chapter inferred that:
1. β-CD and β-CD derivatives (RM β-CD, SBE β-CD, HP β-CD) enhanced the dissolution rate of Nimesulide and accordingly, Nimesulide dosage forms with faster onset of action may be formulated by the use of these Nimesulide-CDs binary systems. Different variables were implicated in this concern; CD type and process of preparation.
2. The process of preparation of Nimesulide-β-CD binary systems showed a significant effect on the dissolution profile of Nimesulide and was in the order of:
Kneading > cogrinding > sintering > physical mixture.
The presence of water and mechanical energy provided during kneading increased the contact surface area and lead to a better dispersion of Nimesulide within β-CD.
The solvent used in kneading Nimesulide-β-CD binary systems greatly affected the release rate of the drug and was in the following order:
Hot water > alcohol 50% > water at ambient temperature
3. Although they have approximately the same cavity size, β-CD and its semi-synthetic derivatives showed different potentials in enhancing Nimesulide dissolution profile with an order of:
RM β-CD ≥ SBE β-CD > HP β-CD > β-CD.
The varying potential of different CDs on Nimesulide release profile may be attributed to intrinsic differences between the individual CDs. The higher Nimesulide dissolution profile obtained with RM β-CD, compared to β-CD, may be explained by the decreased polarity of the derivative provided by the hyDROPhobic methyl groups, permitting better interaction with Nimesulide. The higher solubility of this derivative and formation of drug-CD aggregates are also other possible contributing factors.