A REVIEW ON THE SOLID ORAL DOSAGE FORM FOR PEDIATRICS, REGULATORY ASPECTS, CHALLENGES INVOLVED DURING THE FORMULATION, AND TOXICITY OF THE EXCIPIENTS USED IN PEDIATRIC FORMULATION
DOI:
https://doi.org/10.22159/ijap.2023v15i3.47313Keywords:
Pediatric, Solid oral dosage form, Regulatory aspects, Excipients, Toxicity, Pediatric Drug DeliveryAbstract
Designing an appropriate dosage form in medical treatment for the pediatric population is very challenging. The major challenges faced during designing the oral solid dosage form for pediatrics are also the prerequisites for the development of the dosage form, and they are, administering the drug according to the body weight and taste masking which is followed by other factors like the safety of excipients, size of dosage form and so on. Oral solid dosage forms like mini-tablets, soluble films, and orally disintegrating tablets are a few promising dosage forms for use in the pediatric population. The obstacles such as physiological differences between the various age groups, excipient safety, technology requirements, low profitability, clinical trial limitations, and regulatory ambiguity all have an impact on pediatric dosage form development. Recent advancement in the development of pediatrics formulations has been made due to new regulations, more financial opportunities, and novel collaborative research programs. A shift of pattern towards solid oral dosage form and an emphasis on innovative preparations, such as dispersible, flexible, as well as multi-particulate oral solid dose forms, are some of the advancements. Such advancements have allowed for more flexibility of dose, easy administration, and improved medication formulation acceptance in pediatrics. In consideration of dosage forms for pediatrics, issues such as pediatric suitability, excipient selection, prospects for modified drug release formulations or fixed-dose combinations, palatability, and acceptability, as well as challenges were reviewed in the current manuscript.
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Alessandrini E, Brako F, Scarpa M, Lupo M, Bonifazi D, Pignataro V, Cavallo M, Cullufe O, Enache C, Nafria B, Claverol J, De Taeye L, Vermeulen E, Preston J, Tuleu C. Children’s preferences for oral dosage forms and their involvement in formulation research via eptri (European paediatric translational research infrastructure). Pharmaceutics. 2021;13(5):730.
Yellepeddi VK, Vangara KK. Excipients in pediatric formulations: Biopharmaceutical and toxicological considerations. Excip Appl Formul Des Drug Deliv. 2015; 2(2): 497–519.
Lajoinie A, Henin E, Kassai B, Terry D. Solid oral forms availability in children: A cost saving investigation. Br J Clin Pharmacol. 2014;78(5):1080–9.
Ivanovska V, Rademaker CMA, Van Dijk L, Mantel-Teeuwisse AK. Pediatric drug formulations: A review of challenges and progress. Pediatrics. 2014;134(2):361–72.
Galande AD, Khurana NA, Mutalik S. Pediatric dosage forms-challenges and recent developments: A critical review. J Appl Pharm Sci. 2020;10(7):155–66.
Mfoafo KA, Omidian M, Bertol CD, Omidi Y, Omidian H. Neonatal and pediatric oral drug delivery: Hopes and hurdles. Int J Pharm. 2021;597:20296.
Rouaz K, Chiclana-Rodríguez B, Nardi-Ricart A, Suñé-Pou M, Mercadé-Frutos D, Suñé-Negre JM, Pérez-Lozano P, García-Montoya E. Excipients in the paediatric population: A review. Pharmaceutics. 2021;13(3):387.
Zisowsky J, Krause A, Dingemanse J. Drug development for pediatric populations: Regulatory aspects. Pharmaceutics. 2010;2(4):364–88.
EMA / Committee for Medicinal Products for human use (CHMP) / Paediatric Committee (PDCO). Guideline on Pharmaceutical Development of Medicines for Paediatric Use, EMA (European Medicines Agency) [Internet]. 2017;44(August 2013):1–23 [cited 2022 Dec 02].Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/07/WC500147002.pdf
Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Food and Drug Administration Guidance for Industry: The Content and Format for Pediatric Use Supplements [Internet]; 2005:1-18 [cited 2022 Dec 02]. Available from: https://www.fda.gov/files/drugs/published/Guidance-for-Industry-(Draft)--How-to-Comply-with-the-Pediatric-Research-Equity-Act--(posted-9-7-2005).pdf
Archive.bio.org [Internet]. Biotechnology Innovation Organization: History of Pediatric Studies, Rule, Legislation and Litigation [cited 2022 Dec 02]. Available from: https://archive.bio.org/advocacy/letters/history-pediatric-studies-rule-legislation-and-litigation
Best Pharmaceuticals for Children Act - BPCA [Internet]. NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development [cited 2022 Dec 02]. Available from: https://www.nichd.nih.gov/research/supported/bpca
Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Food and Drug Administration Guidance for Industry: Recommendations for Complying with the Pediatric Rule (21 CFR 314.55(a) and 601.27(a)) [Internet]; c2000 [cited 2022 Dec 02]. Available from: https://www.federalregister.gov/documents/2000/12/04/00-30697/draft-guidance-for-industry-on-recommendations-for-complying-with-the-pediatric-rule-availability
Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Food and Drug Administration Guidance for Industry: How to Comply with the Pediatric Research Equity Act (Draft Guidance) [Internet]; c2019 [cited 2022 Dec 02]. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/how-comply-pediatric-research-equity-act
U.S. Food and Drug Administration [Internet]. Department of Health & Human Service, Food and Drug Administration Memorandum – Establishment of the Pediatric Review Committee (PeRC); c2018 [cited 2022 Dec 02]. Available from: https://www.fda.gov/drugs/development-resources/pediatric-review-committee-perc
European Medicines Agency [Internet]. ICH topic E11. Note for guidance on Clinical investigation of medicinal prodcuts in the paediatric population; c2001 [cited 2022 Dec 02]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human-use_en-1.pdf
Thomas KB, Joergensen M, Lynch G, Rubison M, Porter BD, Sayers J, Tesch C. Clinical Trial Disclosure: Global Overview and Implications of New Laws and Guidelines. Ther Innov Regul Sci. 2010;44(3):213–25.
European Medicines Agency [Internet]. The European paediatric initiative: History of the Paediatric Regulation; c2007 [cited 2022 Dec 02]. Available from: https://www.ema.europa.eu/en/documents/other/european-paediatric-initiative-history-paediatric-regulation_en.pdf
Official Journal of the European Communities [Internet]. Council Resolution of 14 December 2000 on paediatric medicinal products [cited 2022 Dec 02]. Avaialble from: https://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:C:2001:017:0001:0001:EN:PDF
EUR-Lex [Internet]. Regulation (EC) No 1901/2006 Of The European Parliament And Of The Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004. Off J Eur Union; c2006 [cited 2022 Dec 02];378/1-378/19. Available from: https://eur-lex.europa.eu/eli/reg/2006/1901/oj
Cram A, Breitkreutz J, Desset-Brèthes S, Nunn T, Tuleu C. Challenges of developing palatable oral paediatric formulations. Int J Pharm. 2009;365(1–2):1–3.
Preis M. Orally Disintegrating Films and Mini-Tablets—Innovative Dosage Forms of Choice for Pediatric Use. AAPS PharmSciTech. 2015;16(2):234–41.
Zuccari G, Alfei S, Marimpietri D, Iurilli V, Barabino P, Marchitto L. Mini-Tablets: A Valid Strategy to Combine Efficacy and Safety in Pediatrics. Pharmaceuticals. 2022;15(1):108.
Aleksovski A, Dreu R, Gašperlin M, Planinšek O. Mini-tablets: A contemporary system for oral drug delivery in targeted patient groups. Expert Opin Drug Deliv. 2015;12(1):65–84.
Emea European Medicines Agency [Internet]. Reflection Paper: Formulations of Choice for the Paediatric Population. 2006 [cited 2023 Feb 15];(7):1–45. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-formulations-choice-paediatric-population_en.pdf
Nunn T, Williams J. Formulation of medicines for children. Br J Clin Pharmacol. 2005;59(6):674–6.
Jacqz-Aigrain E, Choonara I. Paediatric Clinical Pharmacology. Br J Clin Pharmacol. 2006;78(5):1080–9.
Garvie PA, Lensing S, Rai SN. Efficacy of a pill-swallowing training intervention to improve antiretroviral medication adherence in pediatric patients with HIV/AIDS. Pediatrics. 2007;119(4):893–9.
Spomer N, Klingmann V, Stoltenberg I, Lerch C, Meissner T, Breitkreutz J. Acceptance of uncoated mini-tablets in young children: Results from a prospective exploratory cross-over study. Arch Dis Child. 2012;97(3):283–6.
Thomson SA, Tuleu C, Wong IC, Keady S, Pitt KG SA. Minitablets: new modality to deliver medicines to preschool-aged children. Pediatrics. 2009;235–8.
Kristensen HG. WHO guideline development of paediatric medicines: Points to consider in pharmaceutical development. Int J Pharm. 2012;435(2):134–5.
Faisal M, Cawello W, Burckhardt BB, Laer S. Model-dependent pharmacokinetic analysis of enalapril administered to healthy adult volunteers using orodispersible minitablets for use in pediatrics. Drug Des Devel Ther. 2019;13:481–90.
Khan D, Kirby D, Bryson S, Shah M, Rahman Mohammed A. Paediatric specific dosage forms: Patient and formulation considerations. Int J Pharm. 2022;616:121501.
Thabet Y, Klingmann V, Breitkreutz J. Drug Formulations: Standards and Novel Strategies for Drug Administration in Pediatrics. J Clin Pharmacol. 2018;58:S26–35.
Lura A, Luhn O, Suarez Gonzales J, Breitkreutz J. New orodispersible mini-tablets for paediatric use – A comparison of isomalt with a mannitol based co-processed excipient. Int J Pharm. 2019;572:118804.
Ravinder K, Pawan K, Gaurav S, Paramjot K, Gagan S, Appramdeep K. Orally disintegrating tablets - Friendly to pediatrics and geriatrics. Pharmacia [Internet]. 2010 [cited 2022 Dec 02];2(2):208–20. Available from: http://scholarsresearchlibrary.com/ABR-vol1-iss2/ABR-2010-1-2-87-90.pdf
Kole SS, Kuchekar AB, Limaye DA. Advancements in Formulation Approaches to Pediatric Oral Drug Delivery Systems. Hacettepe Univ J Fac Pharm. 2021;41(4):254–65.
Lopes CM, Lobo JMS, Pinto JF, Costa P. Compressed mini-tablets as a biphasic delivery system. Int J Pharm. 2006;323(1–2):93–100.
M. D, C. P, M. S. Taste Masking By Hot Melt Extrusion Without Loss of Bioavailability for Pediatrics. Int J Pharm Pharm Sci. 2019;11(7):7–13.
Nagaraju T, Gowthami R, Rajashekar M, Sandeep S, Mallesham M, Sathish D, Shravan Kumar Y. Comprehensive Review On Oral Disintegrating Films. Curr Drug Deliv. 2013;10(1):96–108.
Lopez FL, Ernest TB, Tuleu C, Gul MO. Formulation approaches to pediatric oral drug delivery: Benefits and limitations of current platforms. Expert Opin Drug Deliv. 2015;12(11):1727–40.
Lodhi Ds, Singh Panwar A, Golani P, Verma M. A Review of the Combination of Xanthine and Bronchodilator Drug in Mouth‑Dissolving Film for Asthma Treatment. Asian J Pharm Clin Res. 2021;14 (11):24–9.
Shruthi B. K., V. Chandrakala SS. Formulation And Evaluation Of Mouth-Dissolving Film Of An H1 Antihistamine Drug. Int J Cur Pharm Res.2019; 14(6):55-66.
Irfan M, Rabel S, Bukhtar Q, Qadir MI, Jabeen F, Khan A. Orally disintegrating films: A modern expansion in drug delivery system. Saudi Pharm J. 2016;24(5):537–46.
Renu, Jyoti Dahiya, Pawan Jalwal BS. Chewable Tablets: A Comprehensive Review. The Pharma Innovation J 2015; 4(5): 100-105.
Narang AS, Boddu SH. Excipient applications in formulation design and drug delivery. In: Ajit S Narang, Sai HS. Boddu, editors. Excip Appl Formul Des Drug Deliv. Switzerland: Springer Cham; 2015. p.1–10.
an Riet-Nales DA, Kozarewicz P, Aylward B, de Vries R, Egberts TCG, Rademaker CMA, Schobben AFAM. Paediatric Drug Development and Formulation Design—a European Perspective. AAPS PharmSciTech. 2017;18(2):241–9.
Zajicek A, Fossler MJ, Barrett JS, Worthington JH, Ternik R, Charkoftaki G, Lum S, Breitkreutz J, Baltezor M, Macheras P, Khan M, Agharkar S, MacLaren DD. A report from the pediatric formulations task force: Perspectives on the state of child-friendly oral dosage forms. AAPS J. 2013;15(4):1072–81.
Yochana S, Yu M, Alvi M, Varenya S, Chatterjee P. Pharmaceutical excipients and pediatric formulations. Chim Oggi/Chemistry Today. 2012;30(5):56–61.
Kaguelidou F, Kassai Koupai B, Durrieu G. Pediatric pharmacology. Therapie [Internet]. 2018 [cited 2022 Dec 02];73(2):111–2. Available from: https://www.edicionesjournal.com/Papel/9789874922236/Farmacología+pediátrica
Nakamura S, Tanaka C, Yuasa H, Sakamoto T. Utility of Microcrystalline Cellulose for Improving Drug Content Uniformity in Tablet Manufacturing Using Direct Powder Compression. AAPS PharmSciTech. 2019;20(4):151.
Zhang D, Rumondor ACF, Zhu W, Colace T, Marota M, Mora J, Liu Z, Li Y. The Development of Minitablets for a Pediatric Dosage Form for a Combination Therapy. J Pharm Sci. 2020;109(12):3590–7.
Belayneh A, Tadese E, Molla F. Safety and biopharmaceutical challenges of excipients in off-label pediatric formulations. Int J Gen Med. 2020;13:1051–66.
Peire Garcia M. Pediatric pharmacology. Ediciones J [Internet]. 2019 [cited 2022 Dec 02];274. Available from: https://www.edicionesjournal.com/Papel/9789874922236/Farmacología+pediátrica
Warren F. Handbook of Pharmaceutical Excipients. Am J Heal Pharm. 1987;44(8):1946–8.
Balbani APS, Stelzer LB, Montovani JC. Pharmaceutical excipients and the information on drug labels. Braz J Otorhinolaryngol. 2006;72(3):400–6.
Batchelor HK, Marriott JF. Formulations for children: Problems and solutions. Br J Clin Pharmacol. 2015;79(3):405–18.
Allam KVI, Kumar GP. Colorants - the cosmetics for the pharmaceutical dosage forms. Int J Pharm Pharm Sci. 2011;3(Suppl. 3):13–21.
Cheng D, Tan T, Mei Y, Mount S, Galella E, Mitra B, Charlton S, Kuhli M, Ternik R, Walsh J, Rajapakshe A, Thompson K, Mehrotra S, Santangelo M, Liu J, Dixit T, Schaufelberger D, Jamzad S, Klein S, Hoag SW, Wang J, Pfuma E, Khurana M, Alexander J, Radden E, Sood R, Selen A. European Journal of Pharmaceutics and Biopharmaceutics Pediatric formulation development – Challenges of today and strategies for tomorrow : Summary report from M − CERSI workshop 2019. Eur J Pharm Biopharm. 2021;164:54–65.
Ernest TB, Elder DP, Martini LG, Roberts M, Ford JL. Developing paediatric medicines: identifying the needs and recognizing the challenges. J Pharm Pharmacol. 2010;59(8):1043–55.
Conroy S. Paediatric pharmacy - Drug therapy. Hosp Pharm. 2003;10(2):49–57.
Orubu ESF, Tuleu C. Medicines for children: Flexible solid oral formulations. Bull World Health Organ. 2017;95(3):238–40.
Klingmann V, Linderskamp H, Meissner T, Mayatepek E, Moeltner A, Breitkreutz J, Bosse HM. Acceptability of Multiple Uncoated Minitablets in Infants and Toddlers: A Randomized Controlled Trial. J Pediatr. 2018;201:202-207.
Salunke S, Hempenstall J, Kendall R, Roger B, Mroz C, Nunn T, Tuleu C. European Paediatric Formulation Initiative’s (EuPFI) 2nd conference commentary-Formulating better medicines for children. Int J Pharm. 2011;419(1–2):235–9.
Helin-Tanninen M. Extemporaneous Preparation Of Paediatric Oral Formulations Studies conducted in nifedipine powders, capsules and suspensions in a hospital pharmacy [Internet]. 2008 [cited 2022 Dec 02]: [about 59 p.]. Available from: https://core.ac.uk/download/pdf/15168083.pdf
Remove 69th ref
Strickley RG, Iwata Q, Wu S, Dahl TC. Pediatric drugs - Review of commercially available oral formulations. J Pharm Sci. 2008;97(5):1731–74.
Hoppu K. Editorial: Can we get the necessary clinical trials in children and avoid the unnecessary ones? Eur J Clin Pharmacol. 2009;65(8):747–8.
Joseph PD, Craig JC, Caldwell PHY. Clinical trials in children. Br J Clin Pharmacol. 2015;79(3):357–69.
Viergever RF, Karam G, Reis A, Ghersi D. The quality of registration of clinical trials: Still a problem. PLoS One. 2014;9(1).
De Angelis C, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R, Kotzin S, Laine C, Marusic A, Overbeke AJPM, Schroeder T V., Sox HC, Van Der Weyden MB. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. Hypertension. 2005;45(4):631–2.
Thomson D, Hartling L, Cohen E, Vandermeer B, Tjosvold L, Klassen TP. Controlled trials in children: Quantity, methodological quality and descriptive characteristics of pediatric controlled trials published 1948-2006. PLoS One. 2010;5(9):1–9.
De Vries TW, Van Roon EN. Low quality of reporting adverse drug reactions in paediatric randomised controlled trials. Arch Dis Child. 2010;95(12):1023–6.
Chalmers I, Glasziou P. Avoidable waste in the production and reporting of research evidence. Obstet Gynecol. 2009;114(6):1341–5.
Cramer, K., Wiebe,. Moyer, V., Hartling L., Williams K., Swingler G., Klassen T. Children in reviews: Methodological issues in child-relevant evidence syntheses. BMC Pediatr. 2005; 38 (5).
Young B., Shilling V., Hickey H., Sowden E., Smyth R., Williamson P. What parents think about being approached about children’s trials, how this differs from what practitioners expect, and what this tells us about enhancing recruitment. Trials. 2011;12(S1).
Malkawi WA, Alrafayah E, Alhazabreh M, Abulaila S, Al-Ghananeem AM. Formulation Challenges and Strategies to Develop Pediatric Dosage Forms. Children. 2022;9(4):488.
Salazar JC. Pediatric clinical trial experience: Government, child, parent and physician’s perspective. Pediatr Infect Dis J. 2003;22(12):1124–7.
Ackerman TF. The ethics of drug research in children. Paediatr Drugs. 2001;3(1):29–41.
O’Lonergan TA, Milgrom H. Ethical considerations in research involving children. Curr Allergy Asthma Rep. 2005;5(6):451–8.
Truog RD, Rockoff MA. Ethical issues in pediatric anesthesia. Semin Anesth. 1991;10(3):187–94.
Dixon-Woods M, Ashcroft RE, Jackson CJ, Tobin MD, Kivits J, Burton PR, Samani NJ. Beyond “misunderstanding”: Written information and decisions about taking part in a genetic epidemiology study. Soc Sci Med. 2007;65(11):2212–22.
Altavilla A. Pediatric clinical trials. Leg Forensic Med. 2013;1127–36.
Klassen TP, Hartling L, Craig JC, Offringa M. Children are not just small adults: The urgent need for high-quality trial evidence in children. PLoS Med. 2008;5(8):1180–2.
Hill P. Off licence and off label prescribing in children: Litigation fears for physicians. Arch Dis Child. 2005;90(SUPPL. 1).
91. ClinicalTrials.gov. KONCERT A Kaletra ONCE Daily Randomised Trial of the Pharmacokinetics, Safety and Efficacy of Twice-daily Versus Once-daily Lopinavir/Ritonavir Tablets Dosed by Weight as Part of Combination Antiretroviral Therapy in Human Immunodeficiency Virus-1 (HIV-1). United States National Library of Medicine; 2010. Available from: https://clinicaltrials.gov/show/NCT01196195 . [Last accessed on 15 Feb 2023]
ClinicalTrials.gov. Investigating Safety, Tolerability, Efficacy and PK of Olaparib in Pediatric Patients With Solid Tumours. United States National Library of Medicine; 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT04236414 . [Last accessed on 15 Feb 2023]
ClinicalTrials.gov. Study of Entrectinib (RxDx-101) in children and adolescents With Loccaly Advanced Or Metastatic Solid Or Primary CNS tumors And/Or Who Have No Satisfactory Treatment Options (STARTRK-NG). United States National Library of Medicine; 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT02650401 .[Last accessed on 15 Feb 2023]
ClinicalTrials.gov. Study of Finerenone to Investigate a Paediatric Formulation in Healthy Male Voulnteers. United States National Library of Medicine; 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT02956109 . [Last accessed on 15 Feb 2023]
ClinicalTrials.gov. Ondansetron Oral Versus Orally Disintegrating Tablets (ODT). United States National Library of Medicine; 2014. Available from: https://clinicaltrials.gov/ct2/show/NCT02174874 . [Last accessed on 15 Feb 2023]
ClinicalTrials.gov. A Study to Evaluate the Safety and Tolerability of Rizatriptan for Long Term Treatment of Acute Migrane in Children and Adolescents (MK-0462-086 AM3). United States National Library of Medicine; 2012. Available from: https://clinicaltrials.gov/ct2/show/NCT01004263 . [Last accessed on 15 Feb 2023]
ClinicalTrials.gov. A Study to Assess the Efficacy and Safety of Mebendazole for the Treatment of Helminth Infections in Pediatric Participants. United States National Library of Medicine; 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT02034162 . [Last accessed on 15 Feb 2023]
ClinicalTrials.gov. Study of the Safety and Pharmacikinetics of Montelukast (MK-0476) in the treatment of Japanese Pediatric Participants With Perennial Allergic Rhinitis (MK-0476-520). United States National Library of Medicine; 2014. Available from: https://clinicaltrials.gov/ct2/show/NCT01852812 . [Last accessed on 15 Feb 2023]
ClinicalTrials.gov. The Effect of Montelukast on Difficulty in Breathing After Exercise in Pediatric Patients (MK0476-377) (COMPLETED). United States National Library of Medicine; 2011. Available from: https://clinicaltrials.gov/ct2/show/NCT00534976 . [Last accessed on 15 Feb 2023]
ClinicalTrials.gov. Pharmacokinetics, Safety and tolerability of fevipiprant Delivered Via a Once Daily Chewable tablet in Children Aged 6 to < 12 Years With Asthma. United States National Library of Medicine; 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT03650400 . [Last accessed on 15 Feb 2023]
ClinicalTrials.gov. A study of the safety, tolerability, and Antiretroviral Activity of Raltegravir (MK-0518) in Combination With Other Retroviral Therapies in Russian Children and Adolescents Infected With Human Immunodeficiency Virus (HV-1) (MK-0518-248). United States National Library of Medicine; 2014. Available from: https://clinicaltrials.gov/ct2/show/NCT01717287 . [Last accessed on 15 Feb 2023]
ClinicalTrials.gov. Safety and Pharmacokinetics (PK) of Raltegravir in HIV (Human Immunodeficiency Virus)- Infected Children and Adolescents. United States National Library of Medicine; 2007. Available from: https://clinicaltrials.gov/ct2/show/NCT00485264 . [Last accessed on 15 Feb 2023]
ClinicalTrials.gov. Atorvastatin Three Year Pediatric Study. United States National Library of Medicine; 2009. Available from https://clinicaltrials.gov/ct2/show/NCT00827606 . [Last accessed on 15 Feb 2023]
ClinicalTrials.gov. The Role of Lactobacillus Reutri in Children and Adolescents With Anorexia Nervosa. United States National Library of Medicine; 2013. Available from: https://clinicaltrials.gov/ct2/show/NCT02004288 . [Last accessed on 15 Feb 2023]
ClinicalTrials.gov. Phase I Study Of Mebendazzole Therapy for Recurrent/Progressive Pediatric Brain Tumors. United States National Library of Medicine; 2015. Available from: https://clinicaltrials.gov/ct2/show/NCT02644291 . [Last accessed on 15 Feb 2023]
Karen Casidy Thompson, Kimberly Nicole Kaighn, Indra Neil Mukherjee, Catherine Elizabeth, Diimmler Hedy, Tepplier Weiser Christopher Mancinelli, Inventor. Merck Sharp and Dohme LLC, assignee; Taste-masked formulations of raltegravir. Europe patent EP2699094A1; 2014.
Ryo Kojima, Toshiro Sakai, Ryota AZUMA, Marina TANAKA, Inventor. Astellas Pharma Inc, assignee; Pharmaceutical composition for oral administration. United States patent US20210346392A1; 2021.
Saurabh Gupta, Saiesh P. Phaldesai, NSK. Senthil Kumar, Milind Vinayak Sathe, Inventor. Unichem Laboratories Ltd, assignee; Tofacitinib orally disintegrating tablets. United States patent US10034882B2; 2018.
Toshihiro Shimizu, Shuji Morimoto, Tetsuro Tabata, Inventor. Takeda Pharmaceutical Co Ltd, assignee; Orally disintegrable tablets. United States patent US9901546B2; 2018.
Takafumi Sato, Motohiro Ota, Makoto Kigoshi, Hideki Morita, Inventor. Kyowa Kirin Co Ltd, assignee; Taste-masked formulations of raltegravir. United States patent US9861577B2; 2018.
111.Jules Jacob, Kelly CAPUTO Micael Guillot, Kenneth J. Sultzbaugh, Thomas G. WEST, Inventor. Aprecia Pharmaceuticals LLC, assignee; Rapidly Dispersible Dosage Form with High Drug Content. United States patent US20180296479A1; 2018.
Zheng Yi, Inventor. Jiangsu Huhong biomedical Co., Ltd, assignee; Amlodipine besylate orally disintegrating tablet prepared through 3D printing and preparation method of orally disintegrating tablet. China patent CN107823153A; 2018.
Zheng Yi, Inventor. Huhong Ind Shanghai Co Ltd, assignee; Preparation method of olanzapine orally disintegrating tablet based on inkjet 3D printing. China patent CN110269844A; 2019.
David Cochran, Vipul dave, Gregory Koll, Gerard P. Mcnally, Christopher Ee. Szymczak, Stephen Ulrich, Inventor.Johnson and Johnson Consumer Inc, assignee; process for making tablet using radiofrequency and lossy coated particles. Australia patent AU2020201762A1; 2020.
Bengt Arvid Westrin, Inventor. LTS Lohmann Therapie Systeme GmbH and Co KG Acucort AB, assignee; Dexamethasone oral film. United States patent US20190175617A1; 2019.
Robert K Yang, Richard C., Fuisz, Garry L Myers, Joesph M. Fuisz, Inventor. Aquestive Therapeutics Inc, assignee; Uniform Films for rapid dissolving doasage form incorporating taste-masking compositions. United States patent US20190380973A1; 2019.
Manesh A Dixit, Vaibhav Pawar, Rushi Patel, Mineshkumar Patel, Inventor. First Time US Generics LLC, assignee; Abuse deterrent soft chewable drug formulations. United States patent US20190000766A1; 2019.
118.Ngoc minh Nguyen, Lee Yong Lim, Inventor. University of Western Australia, assignee; Taste masking product. United States patent US20190350850A1; 2019.
Ovidiu Romanoschi, Caryn Oryniak, Lius C Muniz, Hiep Huatan, nazim Kanji, Huw Jones, Lindsey Bagley, Graham Godfrey, Inventor. Church and Dwight Co Inc, assignee; multicomponent gummy compositions with hard core. United States patent US20200000716A1; 2020.
Moshe Laudon, Nava Zisapel, Inventor. Neurim Pharmaceuticals 1991 Ltd, assignee; Melatonin mini-tablets and method of manufacturing the same. United States patent US20190060277A1; 2019.
Alfred Chi Yeh Liang, Venkataramana Dingari, Inventor. Ferring BV, assignee; Oral Pharmaceutical compositions of mesalazine. United States patent US20190105275A1; 2019.
122.Surya Prakash Ayalasomayajula, Masha Berkhin, Christopher Bush, Fabian Chen, Bernd Trueby, gesine Winzenburg, Inventor. Novartis AG, assignee; Galenic formualtions of organic compounds. Australia patent AU2019280026A1; 2020.
Catherine Guittet, Luc-Andre Granier, Caroline Roussel-Maupetit, Inventor. Advicenne, assignee;Pharmaceutical composition comprising citrate and bicarbonate salts, and use thereof for treating cystinuria. United States patent US9636304B2; 2017.
Eleni Dokou, Shahla Jamzad, John P. Caesar, Jr., Majed Fawaz, Laura Das, Chong-Hui Gu, Patricia Nell Hurter, Meghna Jai Israni, Meghan M. Johnston, Dragutin Knezic, Andrew G. Kuzmission, Hongren Wang, Inventor. Vertex Pharmaceuticals Inc, assignee; Pharmaceutical composition and administrations thereof. United States patent US20190274959A1; 2019.
International Conference on H. Guidance for Industry E11 Clinical Investigation of Medicinal Products in the Pediatric Population [Internet]. Vol. 65, Federal Register. 2000 [cited 2023 Feb 15]. p. 19777–81. Available from: https://www.fda.gov/regulatory-information/search-fdaguidance-documents/e11-clinical-investigation-medicinal-products-pediatric-population
Karavasili C, Gkaragkounis A, Fatouros DG. Patent landscape of pediatric-friendly oral dosage forms and administration devices. Expert Opin Ther Pat. 2021;31(7):663–86.
Emea. Guideline on Pharmaceutical Development of Medicines for Paediatric Use Guideline on Pharmaceutical Development of Medicines for Paediatric Use. Vol. 44, Emea. 2013 [cited 2023 Feb 15]. p. 1–23. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-pharmaceutical-development-medicines-paediatric-use_en.pdf
Drugs.com [Internet].Tregretol; 2021 [cited 2022 Dec 02]. Available from: https://www.drugs.com/tegretol
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Copyright (c) 2023 SUSHMITA SANKESHWARI, GANGADHARAPPA H. V., ASHA SPANDANA K. M., ANU ELIYAS, SHAILESH THIRUMALESHWAR, PYDA VENKATA HARSHA VARDHAN
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