الفهرس 
Formulation and Evaluation of Antihyperlipidemic Drug in Oral Disintegrating Tablets
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Abstract
Summery Despite great developments in drug delivery, the oral route remains the most preferred route of administration due to its ease of administration, accurate dosage, pain avoidance, low cost, and most importantly, patient compliance. Recently, a new technology entered the market of tablets, which is the oral disintegrating tablet (ODT).
This thesis aimed to formulate and evaluate PITA-ODTs using different co-processed excipients via direct compression. The best PITA-ODT was selected and reformulated with the addition of LORNO, forming a single ODT comprising both drugs, where this combination can provide great potential for limiting myopathy caused by statin overuse and hence improving patient compliance. An in-vivo study was performed in rats to assess the pharmacokinetic parameters and relative bioavailability (RB) of both drugs in the single ODT compared with the marketed products (Lipidalon® and Lornoxicam®).
Chapter I: Formulation and evaluation of oral disintegrating tablets containing Pitavastatin calcium.
This chapter aimed to formulate and evaluate different ODTs containing PITA using different co-processed excipients via direct compression. The best formula was selected based on the criteria of scoring the fastest DT and highest % PITA dissolved after 10 min (Q10 min) and then subjected to further studies.
Investigations and results obtained in this chapter could be summarized as follows:
• Eight PITA-ODTs were successfully prepared using co-processed excipients via direct compression.
• All prepared PITA-ODTs showed acceptable physical properties according to the Pharmacopeial standards.
• Regarding the in-vitro dissolution study, the results showed that (F2) Pharmaburst® attained the highest Q 10 min, whereas F5 Ludiflash® showed the lowest Q 10 min.
• Based on the criteria of scoring the fastest DT and highest Q 10 min, F2 containing Pharmaburst® was chosen as the best formula.
• The SEM micrograph of F2 showed numerous large voids, which appear to be the inner structure of the tablet.
Chapter II: Formulation and evaluation of a single oral disintegrating tablet containing Pitavastatin calcium and Lornoxicam.
The aim of this chapter was to formulate and evaluate the single ODT comprising PITA and LORNO to achieve the aim of treating myopathy caused by statin overuse.
Investigations and results obtained in this chapter could be summarized as follows:
• Overlay for both PITA and LORNO scanning was carried out and revealed that, at λmax 376 nm of LORNO, there was no reading for PITA, Conversely, at λmax 245 nm of PITA, there was a reading for LORNO, indicating that there was overlapping between the two drugs.
• Second derivative spectroscopy was adopted to measure PITA in the presence of LORNO and the zero crossing method was used to notice the appropriate wavelengths for both drugs.
• The zero-crossing method revealed that the zero-crossing of LORNO was at λ 246.2 nm, so this could be suitable for the measurement of PITA with no interference from LORNO.
• The single ODT (M1) comprising both drugs was successfully prepared via direct compression to achieve the aim of treating myopathy caused by statin overuse.
• The outcomes of the characterization tests performed on the M1 ODT met the pharmacopeial standards.
• The in-vitro dissolution profile of PITA and LORNO from M1 ODT and the marketed products revealed that M1 ODT had Q10 min values higher than that of the marketed products.
Chapter III: In-vivo pharmacokinetic study of the single oral disintegrating tablet containing Pitavastatin calcium and Lornoxicam.
This chapter aimed to assess the pharmacokinetic parameters and relative bioavailability of PITA & LORNO from the M1 ODT in comparison with the marketed products (Lipidalon® 1mg tablets & Lornoxicam® 4 mg tablets).
Twelve male Wistar rats (weighing between 300-350 g) were used for this study. The rats were randomly classified into two groups, each of six animals: group I received the M1 formula with a dose of (1 mg/kg) for PITA, and (1.6 mg/kg) for LORNO, and group II received the marketed products, Lipidalon® (1mg) and Lornoxicam® (4 mg), with equivalent doses of 1 mg/kg for the former and 1.6 mg/kg for the latter, according to rat body weight. The marketed tablets were dispersed in distilled water, where 0.9 mL contained the proper dose of PITA (1 mg/kg) and 1.2 mL contained the needed dose of LORNO (1.6 mg/kg). The M1 ODT containing the adjusted dose of PITA (0.3 mg) and LORNO (0.48 mg) according to rat body weight was prepared via direct compression. A parallel design was followed.
Investigations and results obtained in this chapter could be summarized as follows
• LC-MS/MS was suitable method for the analysis of PITA and LORNO in rat plasma.
• The mean values of Cmax and AUC (0-∞) of the M1 formula were significantly higher (p<0.05) than that of the marketed products (Lipidalon® and Lornoxicam® tablets).
• The mean value of Tmax of the M1 formula was shorter and significantly different (p<0.05) than that of the marketed products.
• The relative bioavailability was 286.7% and 169.73% for PITA and LORNO respectively compared with the market products.
• Based on the AUC (0-∞), Tmax, and % RB values, the M1 formula outperforms the marketed products.