Issue link: https://www.e-digitaleditions.com/i/1101841
The FDA, USP, and the dissolu- tion testing community have been very active in providing increased guidance for tablet and capsule dis- solution. T he areas specif ically include immediate-release dosage forms, disintegration, capsules, split tablets, discriminatory methods, and alcohol dose dumping. FDA guidances The FDA has recently issued a number of useful guidances [1]. For example, the guidance, "Use of Liq- uids and/or Soft Foods as Vehicles for Drug Administration: General Con- siderations for Selection and In Vitro Methods for Product Quality Assess- ments," gives instructions for how to assess the effect on dissolution when the dosage forms are delivered in a vehicle such as apple sauce. The guidance, "Tablet Scoring: Nomen- clature, Labeling, and Data for Evalu- ation," provides the way to compare dissolution results of split versus non- split tablets. The guidance, "Quality Attribute Considerations for Chew- able Tablets," provides instructions for developing a dissolution testing method for chewable tablets. While the FDA guidances, "Drug Products, Including Biological Prod- ucts, that Contain Nanomaterials" and "Liposome Drug Products" are not particularly helpful in providing suggestions for in vitro testing meth- ods for nanomaterials and liposomes, they do give some pertinent infor- mation on these dosage forms. A summary of recent guidances would not be complete without a reference to the finalized guidance, "Dissolution Testing and Acceptance Criteria for Immediate-Release Solid Oral Dosage Form Drug Products Containing High Solubility Drug Substances." This important guid- ance for highly soluble immedi- ate-release dosage forms gives 0.1 N HCL, paddle at 50 rpm (or basket at 100 rpm), 500 milliliters as the pre- scribed conditions and sets the spec- ification at 80 percent in 30 minutes. It also states that showing discrimi- natory power is not necessary for these fast-dissolving dosage forms. USP USP has provided in vitro testing methods for dosage forms other than conventional tablets and capsules in a proposed new chapter, <1711> "Oral Solid Dosage Forms—Disso- lution Testing." The dosage forms discussed in the chapter include effervescent tablets, chewable tab- lets, sublingual tablets, orally disinte- grating tablets, gastroretentive tab- lets, granules or pellets administered with food or beverages, and loz- enges. Another proposed chapter, <1236> "Solubility Measurements," provides instr uctions on how to determine the solubility of drug sub- stances and the composition of biorelevant media. The USP general chapter <701> "Disintegration" has revision proposals that combine and add dosage form testing procedures. USP has also proposed two new monographs for capsule shells: hard gelatin capsule shells and hard hypromellose capsule shells. These monographs have storage conditions and other tests worth examining. These chapters and monograph pro- posals are available for viewing and comment for free at usppf.com. By now, everyone involved with dissolution testing should know about papain and bromelain, the two additional enzymes (along with pep- sin and pancreatin) that can be used in the media when testing cross- linked capsules. The activity of these enzymes is important. Bromelain is listed as a reagent in the reagent specification section in USP, and its activity determination can be found within that description. For papain, there is a monograph, which includes a casein digestive power test. USP is upd ating the premier resource for method development and validation for conventional dos- age forms: <1092> "USP General Informational Dissolution Procedure: Development and Validation." The USP general informational chapter <1088> "In Vitro and In Vivo Evalua- tion of Dosage Form" is also going through an update. Other publications Members of the A APS in vitro release and dissolution testing com- munity have published informative and interesting papers on alcohol dose dumping (DOI: 10.1186/s41120- 017-0014-9), strategy to developing d is c r iminator y method s ( D OI: 10.1208/s12249-018-1197-7), and a review article on USP Apparatus 2 perfor mance verification testing (DOI: 10.14227/DT260119P6). The August 2018 issue of Dissolution Tech- nologies was a special edition of review articles that included the topics of in vivo and in vitro correlations (DOI: 10.14227/DT250318P20), disintegra- tion (DOI: 10.14227/DT250318P30), and fiber optics (DOI: 10.14227/ DT250318P70). T&C Reference 1. https://w w w.fd a.gov/dr ugs / guidancecomplianceregulatoryinfor- mation/guidances/default.htm. Vivian A. Gray is president of V.A. Gray Consulting, Hockessin, DE (vagray@ rcn.com, www.vagrayconsulting.net) and managing director of Dissolution Tech- nologies, a peer-reviewed journal dedi- cated to dissolution testing issues (www. d i s s o l u t i o n t e c h. com). She is also a member of Tablets & Capsules' edito- rial advisory board. b a c k p a g e Recent in vitro release testing activities, including FDA and USP