Preparation Of Oxycodone Acetaminophen Capsules And Evaluation Of Quality Consistency

Objective:The preparation technology,quality control and stability of oxycodone paracetamol capsules were studied in this paper.The bioequivalence test and relative bioavailability of human body were also studied to evaluate the bioequivalence of human body,so as to provide reference for clinical medication.Methods:Refer to the prescription of acetaminophen oxycodone capsule?trade name:taylox?produced by Mallinckrodt Pharmaceutical Co.,Ltd.,the compatibility test between API and excipients was carried out for the used excipients.Prescription screening was carried out with excipients with good compatibility used in the reference preparation.The crushing technology and particle size of acetaminophen were investigated.The content of maize starch was determined by gravimetric method.The types of adhesives,the dosage of lubricants,flow aids,antioxidants and surfactants were investigated.The prescription and process were finally determined.According to the small-scale test,pilot-scale test and production,the batches were gradually enlarged,and the self-made preparations and reference preparations were compared and studied.Referring to Pharmacopoeia and related quality standards,ICH guidelines,a method was established,by determinating paracetamol and oxycodone hydrochloride related substances in this product and the dissolution,content determination and related substance examination methods were verified.The stability of the samples was also investigated.The blood concentration of oxycodone and paracetamol in vivo was determined by LC-MS/MS,and the methodology was validated.By use of single-center,open,randomized and self-crossed control,22 subjects were given self-made oxycodone capsules and Taylor capsules?trade name:taylox?produced by Malinkro Pharmaceutical Company in the United States.The relative bioavailability and bioequivalence of the two preparations were studied.Results:The compatibility between APIs and excipients is good.The capsules produced by the optimized process have high particle density,good fluidity,small weight deviation;rapid disintegration and good reproducibility.The impurities and contents of related substances in self-made preparation and reference preparation are basically the same,the dissolution behavior is basically the same,and the product quality is stable and uniform.A method for the determination of paracetamol and oxycodone hydrochloride related substances was established.The methods for the examination of related substances,dissolution and content determination were specific,sensitive,accurate,precise and well tolerated.The test of influencing factors,accelerated test and long-term stability showed that the products produced by this process were stable,uniform and controllable in quality.These studies provide a basis for quality control and product validity of oxycodone acetaminophen capsules.Amethod for determination of oxycodone in plasma of healthy volunteers by LC-MS/MS internal standard was established.A method for determination of acetaminophen in plasma of healthy volunteers by HPLC internal standard method was established.Endogenous substances and other substances in plasma do not interfere with the sample peak and internal standard peak.The specificity is good.The sensitivity,accuracy,intra-batch and inter-batch precision meet the requirements.The method meets the requirements of biological sample analysis.The confidence intervals of Ln(AUC_0-16h)and LN(AUC_0-?)[1-2a]of oxycodone and acetaminophen were 92.3%-106.4%,98.4%-107.3%and92.4%-106.3%,98.0%-106.9%respectively,in the range of 80%-125%by two one-sided t-test The confidence intervals of ln(C_max)[1-2?]of oxycodone and acetaminophen were 84.9%-110%and 87.8%-110.7%,in the range of80%-125%.The results showed that the two preparationswere bioequivalent.The relative bioavailability F of oxycodone and paracetamol were?101.1±19.94?%and?103.5±11.94?%respectively,whichmetthe requirements of bioavailability.The two preparations were bioequivalent.Conclusion:The preparation process of oxycodone acetaminophen capsules has good reproducibility.The product is safe,effective,stable,uniform and controllable in quality.The self-made preparation is the same as reference preparation in both quality and bioequivalent...