Document Details
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Document Type |
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Thesis |
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Document Title |
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Development and Optimization of Liquisolid Tablets Containing Tadalafil and Dapoxetine as a Combined Therapy for Male Sexual Dysfunction تطوير و استمثال أقراص السائل صلبه تحتوي على عقاري تادالافيل و دابوكستين كعلاج تكاملي للضعف الجنسي لدى الرجال |
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Subject |
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faculty of Pharmacy |
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Document Language |
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Arabic |
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Abstract |
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Liquisolid technique is a promising technique that contributes to improving the dissolution rate of drugs. Liquisolid technique used to convert a liquid into simply compressible, non-adherent and free-flowing dry powder by mixing with chosen appropriate excipients known as carrier material such as cellulose, starch, or lactose and coating material such as silica powder. Liquisolid technique contributes to enhancing the drug release properties hence bioavailability of poorly soluble drugs as a result of observed increase of wetting characteristics and drug surface area available for dissolution.
The aim of this study is to improve the solubility of tadalafil (TDL) and dapoxetine (DPX) and enhance the flowability of the powder blend leading to compression in liquisolid tablets. To achieve our aim, the solubility of TDL and DPX was investigated in different nonvolatile solvents. The solvents used were glycerin, polyethylene glycol (PEG) 200, PEG 400, Span 80, Tween 80, Kolliphore, Labrosal, and distilled water. The holding capacity of the carrier and coating materials was evaluated. Finally, the flowability of the powder mixture was studied by the angle of repose, Hausner ratio and Carr’s index methods. The results displayed that TDL is solubilized highly in PEG 200 whereas DPX is highly solubilized in Labrasol. The powder blend showed suitable holding capacity and had a good flowability especially after the addition of silica powder.
Several formulations of LSTs having 5 mg and 30 mg of TDL and DPX, respectively and with varying ratios of the carrier to coat (i.e., different R values, ranging from 5 to 15) were prepared. Avicel PH 101 and fumed silica were used as a carrier and coat material, respectively, and PEG 200 and Labrasol were used as a nonvolatile liquid to prepare the liquisolid formulations. Box Behnken design was utilized to study and optimize the formulation factors that affect quality attributes and the dissolution behavior of the liquisolid formulations. The post-compression parameters like friability, hardness, drug content, weight uniformity and in vitro drug release were carried out. The values of post-compression parameters for the prepared tablets were found to be within compendia limits. The liquisolid tablets of TDL and DPX revealed a much higher dissolution rate. The optimized combination of independent factors verified the desired hardness, disintegration time, and dissolution efficiency for both TDL and DPX.
This outcome confirmed the reliability of the optimization procedure with regard to shortening the disintegration time, increasing the hardness of the LSTs to fulfil Pharmacopeial requirements and enhancing the dissolution efficiency of TDL and DPX within 60 minutes. The relative bioavailability of TDL was increased with rapid onset of action as reflected by the shorter time required to reach the maximum plasma concentration. This result demonstrates that the onset was rapid enough, and the duration and the concentration achieved a level suitable to overcome male sexual dysfunction. The pharmacokinetic parameters of the clinical study indicated that the maximum plasma concentration (Cmax) of TDL in LSTs was 122.61 ng/ml within 2 h (tmax) compared to the marketed tablets which reach to 91.72 ng/ml after 3 h. These findings indicated that the LST reached the maximum plasma concentration faster than the marketed tablet and consequently produced the rapid onset of therapeutic action. The optimized LS formulation achieved this Cmax of the marketed tablet after only 1 h which revealed that LS formulation improved the rate and extent of TDL absorption compared to the marketed tablet. Also, LST was showed higher AUC in comparison to the marketed tablets. By comparing the relative bioavailability and the pharmacokinetic parameters of the optimized LSTs with the marketed tablets in healthy human volunteers displayed significant improvement in the drug bioavailability after oral administration due to the improvement of drug solubility and subsequently accelerating its absorption. So, the liquisolid technique can be a promising alternative for the formulation of water-insoluble drugs into rapid release tablets. |
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Supervisor |
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Prof. Khaled Mohamed Mohamed El-Sei |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1441 AH
2020 AD |
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Co-Supervisor |
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Dr. Badr Mubarak Al-Juaid |
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Added Date |
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Wednesday, May 27, 2020 |
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Researchers
| فايز عمير العتيبي | Alotaibi, Fayez Omear | Researcher | Master | |
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