Polymorphic gabapentin: thermal behaviour, reactivity and interconversion of forms in solution and solid-state

Novel Challenges in Crystal Engineering: Polymorphs and New Crystal Forms of Active Pharmaceutical Ingredients

“…A patent by Chen et al 71 . describes a new form of gabapentin, dehydrated A, which is consistent with form reported by Reece and Levendis 70 , labelled form IV by Braga and co-workers 68 . Another crystalline form of gabapentin was described by Lladò et al 72 In all characterized forms of gabapentin the molecule crystallizes in its zwitterionic form and hydrogen-bonds consist of charge-assisted N + -H•••O -interactions all the supramolecular arrangements relying on chain motifs.…”

“…In all the three structures, the cyclohexane ring adopts an almost perfect chair conformation. Thermal characterization of the three polymorphs is also reported 68 . In the first DSC heating cycle form II shows an endothermic peak at 158°C ( Figure 5) while in the second heating cycle the endothermic peak is at 87°C, thus representing the melting point of gabapentinlactam 74 , confirmed by recrystallization and second heating cycle from the melt on HSM ( Figure 6).…”

“…A wide range of studies have been performed in the last few years, here we will focus on some of those we have been recently engaged. Several studies with gabapentin, a neuroleptic drug, have been reported [31][32][33][34] and a few multicomponent crystal forms with carboxylic acids have been exploited and will be deeply discussed in this chapter. With the antibiotic 4-aminosalicylic acid (4ASA) some new crystal forms were disclosed, solvates, and molecular salt 35 , showing a clear tendency of this API to form multicomponent crystallines with lone-pair containing heterocycles, such as dioxane, morpholine and piperazine, disrupting the typical R 8 homosynthon in 4ASA ( Figure 1 Gabapentin (1-(aminomethyl)cyclohexane acetic acid, GBP) is an analogue of gammaaminobutyric acid (GABA) and exhibits anticonvulsant properties.…”

“…Changes in solid state structure can have marked influence on the physiological absorption characteristics supporting the search for multicomponents crystal forms as means of improving the limited bioavailability of the drug 7,33,61,62 . Gabapentin is known to exist in three anhydrous polymorphic forms 32,63,64 , which have been the object of many patent applications and issued patents. The nomenclature is not uniform and different publications refer to different forms making use of the same name.…”

Bio-Inspired Metal-Organic Frameworks in the Pharmaceutical World: A Brief Review

“…Cocrystals represent a more recent class of crystal forms that own particular scientific and regulatory advantages (FDA guidance is already available and cocrystals are now being commercialized as drugs in some countries). Many examples show their relevance in the pharmaceutical industry, most of them by enhancing stability, solubility and/or bioavailability of known drugs [7][8][9][10][11][12][13][14][15][16][17][18][19][20].…”