“…43,53,54,58,80,81,86,111,114,117,118,123 If the drug itself is found to be responsible for the pain on injection or tissue damage, the formulator could use a prodrug or salt form; 70,102,120 formulate the drug as a suspension or emulsion rather than as a solution; 43,56,[59][60][61][62]75,85,125 encapsulate the drug in some type of biocompatible/biodegradable carrier such as liposomes, 133 microspheres, 134 or mixed micelles; 63 or develop other novel drug complexes. Formulation changes can also involve modifications in the type of buffer, cosolvents, or other excipients used in the product 70,102,106,125 or altering the final pH of the product. [68][69][70]102 If necessary, the drug product labeling may include a recommendation that a specific vehicle or local anesthetic or other protective agent be administered concurrently with the drug.…”