Pharmaceutical acceptability

Next, reductive amination (step 4 in scheme 1) was exchanged with copper catalyzed palladium coupling (step 2 in scheme 1). Atomic absorption analysis for palladium in RWJ-26240 samples prepared by scheme 2 indicated that the level of palladium was reduced to an acceptable level. This improvement may be due to the two reduction steps subsequent to the use of palladium in scheme 2.177 The final major modification to the reaction scheme was the substitution of NaBH4 for NaBH3CN. The yield of product (60%) was determined by HPLC (Method 2). Reductive alkylation with formalin/NaBH4 afforded a pharmaceutically acceptable drug substance. 

The types of microorganisms found in various products are Pseudomonas species, including Pseudomonas aeruginosa, Salmonella, species, Staphylococcus aureus, and Escherichia coli. The USP and other pharmacopoeias recommend certain classes of products to be tested for specified microbial contaminants, e.g., natural plant, animal, and some mineral products for the absence of Salmonella species, suspensions for the absence of E. coli, and topically administered products for the absence of P. aeruginosa and S. aureus. Emulsions are especially susceptible to contamination by fungi and yeasts. Consumer use may also result in the introduction of microorganisms. For aqueous-based products, it is therefore mandatory to include a preservative in the formulation in order to provide further assurance that the product retains its pharmaceutically acceptable characteristics until it is used by the patient. 

The chemical and physical stability of aqueous and nonaqueous suspensions of a number of solvatomorphs of niclosamide has been evaluated in an effort to develop pharmaceutically acceptable suspension formulations [90]. Studied in this work was the anhydrate, two polymorphic monohydrates, the 1 1, Y, A"-dimethyI I ormam ide solvatomorph, the 1 1 dimethyl sulfoxide solvatomorph, the 1 1 methanol solvato-morph, and the 2 1 tetraethylene glycol hemisolvate. All of the solvatomorphs were found to convert initially to one of the polymorphic monohydrates, and over time converted to the more stable monohydrate phase. The various solvatomorphs could be readily desolvated into isomorphic desolvates, but these were unstable and became re-hydrated or re-solvated upon exposure to the appropriate solvent. 

US patent 6,833,379, Crystal modification of torasemide [119], This invention relates to the characterization of a new crystal modification III of torasemide, to a process for its preparation by the use of controlled acidifying of alkaline solutions of torasemide with inorganic or organic acids with or without addition of a crystal seed, to its use as a raw material for the preparation of the crystal modification I of torasemide and of pharmaceutically acceptable salts of torasemide, as well as to pharmaceutical forms containing this new torasemide crystal modification. 

In contrast to certain oil emulsions (including Incomplete Freund s Adjuvant), the liposphere approach uses pharmaceutically acceptable biodegradable constituents. 

A DDS such as a solid dispersion increases dissolution rate by dispersing the drug either molecularly or in an amorphous state in a water-soluble carrier.9 When given as a solution in a pharmaceutically acceptable organic- or lipid-based solvent that is either... 

A. Lazzarini L. Gastaldo G. Candiani I. Ciciliato D. Losi F. Marinelli E. Selva F. Parent , Antibiotic 107891, Its Factors A1 and A2, Pharmaceutically Acceptable Salts and Compositions, and UseThereot. W02005/014628 A1, 2005. 

Afermuth, C. G and P. H. Stahl. 2002. Selected procedures for the preparation of pharmaceutically acceptable salts. InHandbook of Pharmaceutical Salts Properties, Selection, and Use, edited by P. H. Stahl and C. G. V fermuth, 249-263. New York Wiley-VCH. 

In summary, the goal with respect to size reduction of particles for intravenous usage is to provide an acceptable size range with balance in the desired therapeutic efLcacy, safety, and formulation shelf life. Poorly water-soluble crystalline APIs are becoming increasingly good candidates for the micronization process in the preparation of biocompatible and pharmaceutically acceptable nanoparticulate formulations. 

Analytical precision relative to the amount of degradation is the primary reason that determination of the increase in levels of degradation products rather than loss of potency is recommended. Potency results have been used when degradation well beyond the levels considered pharmaceutically acceptable were studied,... 

S.L. Childs, N. Rodriguez-Hornedo, L.S. Reddy, A. Jayasankar, C. Maheshwari, L. McCausland, R. Shipplett, B.C. Stahly, Screening strategies based on solubility and solution composition generate pharmaceutically acceptable cocrystals of carbamaze-pine, CrystEngComm 10 (2008) 856-864. 

R-(R, R )]-2-(4-fluorophenyl)- 3, 8-dihydroxy-5-(l-methylethyl)-3-phenyl-4-[(phe nylamino)-carbonyl]-lH-pyrrole-l-heptanoic acid or (2R-trans)-5-(4-fluorophenyl)-2-( 1 -methylethyl)-(V,4-diphenyl-l -[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-lH-pyrrole-3-carboxamide or pharmaceutically acceptable salts thereof. 

This begs the question of what effect the transition comprising has in this example. We have already seen that we cannot read the claim to allow addition to structural formula I itself. However, the preamble to the claim clearly explains that a pharmaceutical composition is being claimed and not merely a compound. We do not need to get into the exact nature of any claim construction limitations that this preamble might introduce to appreciate that this claim is not limited in scope to the compound of formula I and at least one pharmaceutically acceptable excipient, but would also cover the addition of materials that might be understood to go into a pharmaceutical composition. If the preamble is understood to be a limitation of the claim, then the claim can be read to be broad enough to capture the compound in a pharmaceutical composition but not so broad as to capture the compound in any possible setting, to ensure this interpretation, the patent drafter has carefully added an additional required element, the pharmaceutically acceptable excipient.19... 

A compound, or pharmaceutically acceptable salt thereof, that is selected from the group consisting of A, B, C, D, and E. 

A compound according to claim 1, and at least one pharmaceutically acceptable excipient. 

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