Preparation And Quality Evaluation Of Ketorolac Tromethamine Orally Disintegrating Tablets

Background and PurposeKetorolac tromethamine is currently the best analgesic effect of the NSAID,but also the only non-steroidal anti-inflammatory drug that can achieve opioid level analgesia,with strong,non-addictive,non-narcotic and other characteristics,usually used for postoperative analgesia,relief of acute traumatic pain and other severe pain[1-4].At present,the ketorolac tromethamine dosage forms marketed in China mainly include injections,tablets,capsules and eye drops.Tablets are the most traditional dosage forms of pharmaceuticals in nature,which are easy to carry and use,realize mechanized production and divide the dose,low cost.However,tablets are pressurized,their bioavailability are lower and disintegrate slowly,so they are difficult to swallow for the elderly,children,mentally ill patients and so on.Therefore,the popularization and use of tablets are limited.In recent years,various immediate-release formulations have become a hot topic in the study of new drug dosage forms,especially orally disintegrating tablets [5-8].Orally disintegrating tablets can quickly disintegrate or dissolve without water in the mouth.Orally disintegrating tablets can disintegrate immediately when they meet saliva,so that the drug dissolve,absorb and work quickly.so it is especially suitable for drugs that need to be acted quickly,such as first aid drugs,nonsteroidal anti-inflammatory drugs,antispasmodic and antiemetic drugs and respond to sudden diseases.Compared with ordinary tablets,orally disintegrating tablets have the advantages of convenient administration,fast onset of action,high bioavailability,and little irritation to the mucosa of the digestive tract.As a new solid immediate-release dosage form,orally disintegrating tablets have received widespread attention from new drug research institutions and pharmaceutical companies around the world.This study combines the pharmacological properties of ketorolac tromethamine with the advantages of the dosage form of orally disintegrating tablets to develop ketorolac tromethamine orally disintegrating tablets,which are especially suitable for acute pain,lack of timely access to water,emergency and other special environments.Disintegration time and texture are two challenges in the design of tablets prescriptions,which limited the development of this new dosage form.In this paper,we used ketorolac tromethamine as a model drug,used the imported high-performance excipients,and the whole powder direct tableting method to prepare industrializable ketorolac tromethamine orally disintegrating tablets,and study its quality standards.Method and Results1.Study on the physicochemical properties of ketorolac tromethamine: the equilibrium solubility of ketorolac tromethamine in p H 1.2 hydrochloric acid solution,p H4.5 phosphate buffer,and p H6.8 phosphate buffer was determined by saturation solubility-high performance liquid chromatography,which was 0.05 mg·m L-1,868.10 mg·m L-1,and 811.03 mg·m L-1;the ketorolac tromethamine acidity was determined.The acidity was 6.25;the stability of ketorolac tromethamine in different p H media was investigated,and ketorolac tromethamine had good stability in p H1.2 hydrochloric acid solution,p H4.5 phosphate buffer,and p H6.8 phosphate buffer.The ketorolac tromethamine is low in p H 1.2 hydrochloric acid solution because it is easy to dissociate to form ketorolac,which is difficult to dissolve in water;2.Premixed excipients for the preparation of ketorolac tromethamine oral collapse tablets: the preparation of ketorolac tromethamine orally disintegrating tablets using premixed excipients,the optimal prescription was screened by orthogonal experiment design method: ketorolac tromethamine 10 mg,aspartame 3mg,blueberry flavor 2mg,Prosolv-ODT 282 mg,magnesium stearate 3mg;3.Preparation and prescription optimization of ketorolac tromethamine orally disintegrating tablets: In order to improve the taste,disintegration performance,compressibility and one-sided cleanliness of the orally disintegrating tablets,and lay a good foundation for the pilot scale-up experiment,the prescription of orally disintegrating tablets was further screened through one-factor experiments,and the prescription of ketorolac tromethamine orally disintegrating tablets was optimized by orthogonal experiment design method,and the optimal prescription was optimized: ketorolac tromethamine 10 mg,aspartam 3mg,blueberry flavor 2mg,mannitol 90 mg,microcrystalline cellulose 150 mg,Croscarmellose sodium 10 mg,magnesium stearate 1.5 mg,tablet weight 266.5 mg / tablet.4.Ketorolac tromethamine orally disintegrating tablets quality standard research: in accordance with the 2020 edition of the Chinese Pharmacopoeia and the "Technical Guidelines for Chemical Drug Research",the quality standard research of ketorolac tromethamine orally disintegrating tablets was carried out,the HPLC method was established to determine the content and dissolution of this product,and the analytical methodological verification was carried out from the aspects of chromatographic conditions and system applicability test,linearity and range,precision,stability,recovery rate,repeatability test,etc.,and the results showed that the establishment of HPLC determination methods was highly exclusive and reproducible.The measurement results are stable and reliable,and can be used for the quality control of ketorolac tromethamine oral collapse tablets.ConclusionIn this paper,the key factors that affecting the use of orally disintegrating tablets were studied and discussed comprehensively,and the balance of disintegrating,flavor masking and taste was solved.Through the quality and preliminary stability study,we find that the orally disintegrating tablets have good taste and disintegration.