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16 Pharmaceutical Technology ® | BioPharm International ® Trends in Manufacturing May 2025 PharmTech.com Non-salt drugs. This discussion identifies sev- eral drug t y pes relevant to compounding calcula- tions; these are categorized per chemical structure as non-salt drugs and salt drugs. Non-salt drugs are also termed free acids or free bases; non-salt drugs have covalent and other non-ionic bonds. For com- pounding purposes, the active moiety of a non-salt drug comprises the entire drug molecule (i.e., active moiety is same as active drug). Salt drugs. Salt drugs are molecules with ionic bonds. Salt drugs are easily recognized by name (e.g., sodium drug, potassium drug, drug hydrochloride, drug acetate, and others that include counterions). Some non-salt drugs may be confused as salts (e.g., clindamycin phosphate is an ester; clindamycin pal- mitate hydrochloride is a salt of an ester). Reviewing the molecule structure is essential to determine the drug type. Some drugs may be available as either non- salt (covalent) molecules or as salts (e.g., phenobarbi- tal and sodium phenobarbital; codeine and codeine phosphate), and either may be used in compounding with appropriate evaluation; their respective proper- ties (i.e., pharmacologic and physicochemical) must be considered. Policy-exception salts. Another type of salt drug, policy-exception salts, has also been identified. These molecules are specified in the United States Pharmaco- peia (USP)/FDA salt policy and are dosed differently than salt molecules. Policy-exception salts require different calculations and labeling than salt drugs that comply with policy. Recognizing salt molecule structures is also important in electrolyte calcula- tions. Peptides. Peptides may be small-molecule drugs or biologics depending on their amino acid chain length (<40 amino acids are small molecules; >40 amino acids are biologic proteins). Peptides have covalent bonds bet ween a m i no acids as wel l as ion izable groups and salts. FDA is currently reviewing data to definitively classif y peptides within compounding bulk lists (12,13). Drug forms. This discussion also identifies several drug forms relevant to compounding calculations. Forms describe the concentration of drug moiety in the drug. Forms may be bulk solids assumed to be es- sentially 100% potent or pure; pharma industry and 503B outsourcing facilities commonly use bulk drugs for compounding. Forms may also be drugs at some concentration in solid or liquid mixtures; 503A hospi- tal and community pharmacies are more likely to use drug mixtures (e.g., commercial sterile IV additives and commercial tablets) as drug sources for individ- ual unit compounding. Commercial products used in compounding also contain functional formulation ingredients (filler, binder, coating, f lavor, color, etc.) (14). These ingredients must be evaluated before use; they may cause undesirable effects on patients (e.g., allergic reactions, lactose intolerance), be restricted by religious beliefs (15), or have incompatible phys- icochemical properties. Part two in this series will address numeric bulk drug calculations; part three will address numeric drug mixture calculations. Atomic mass. The atomic mass (atomic weight) is the mass of an individual element expressed in atomic mass units (amu) or daltons (Da) (e.g., sodium = 22.99 amu). Atomic masses represent protons and neutrons in the atom structure; the atomic number represents protons; atom ic mass decima ls repre- sent atom isotopes. The molecular mass (molecular weight) (MW) of a compound is the combined masses of individual elements, hydrates, solvates, and other molecule components (e.g., sodium chloride MW = Na + Cl = 58.44 amu). The active moiety molecular mass may be calculated based on the atomic weights of the individual elements in the active moiety. Also rele- vant is the number of active moiety components in the drug molecule (e.g., divalproex sodium contains t wo valproic acid active moieties). The molecular masses of the active moiety and drug are correlated to their respective gravimetric weights by calculat- ing moles (mols) and millimoles (mmols). A mole is the weight in grams of the drug molecular mass (e.g., 58.44 grams = 1 mole of NaCl; 58.44 mg = 1 mmol of NaCl). Understanding moles is important to deter- mine equivalent dosages of different drug salts. Non-proprietary name. The most relevant drug name in compounding is the non-proprietary name. The non-proprietary name is the generic name of the drug; diazepam is a non-proprietary name. Non-pro- prietary names are approved by country regulatory agencies and the World Health Organization (WHO) and usually include a drug-name stem; (e.g., -caine [local anesthetics], -olone [steroids], and many others) (16). Proprietary drug names are commercial market- ing names; Valium is a proprietary name. Pharmaceutical alternatives. Pharmaceutical al- ternatives are drugs that have the same active moi- ety but are a different molecule (i.e., different salts or esters). Metronidazole is an active moiety; metro- nidazole hydrochloride and metronidazole benzoate are pharmaceutical alternatives. The same moles of pharmaceutical alternatives have the same pharma- cologic effect (e.g., same moles of codeine, codeine sulfate, and codeine phosphate have different grav- imet r ic weights but sa me pha r macologic ef fect). Pharmaceutical alternatives used for compounding must be approved drugs—not unapproved synthetic salts. Different drug salts may have different prop- erties (solubility, pKa, lipophilicity, hygroscopicity, others [17]); substituting pharmaceutical alternatives requires evaluation of respective physicochemical properties. Pharmaceutical alternative dosages are COMPOUNDING