We have received a special prescription: gabapentin 5% in Cetomacrogol cream. How best to tackle this in terms of processing and stability?

references

Gabapentin is described as L-(aminomethyl) cyclohexaneacetic acid with a molecular formula of C9H17NO2 and a molecular weight of 171.24. The structural formula of Gabapentin is: Gabapentin is a white to off-white crystalline solid with a pKa1 of 3.7 and a pKa2 of 10.7. It is freely soluble in water and both basic and acidic aqueous solutions. The log of the partition coefficient (n-octanol/0.05 M phosphate buffer) at pH 7.4 is-1.25.

Storage (Neurontin Oral Solution): Store refrigerated, 2 °-8 °C (36 °-46 °F)

Stability studies of gabapentin in aqueous solutions.

Zour E, Lodhi SA, Nesbitt RU, Silbering SB, Chaturvedi PR. Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Morris Plains, New Jersey 07950.

Abstract Gabapentin is a gamma-aminobutyric acid analogue, which has been shown to be an effective antiepileptic. The solution stability of gabapentin in buffered systems was studied in order to facilitate the formulation of a liquid product. The degradation of the drug was followed as a function of pH, buffer concentration, ionic strength, and temperature. The results indicated that the rate of degradation was proportional to the buffer concentration and temperature. The pH-rate profile of gabapentin degradation showed that the rate of degradation was minimum at an approximate pH of 6.0. Further, the data suggested a of solvent-catalyzed degradation rate for the zwitterionic species compared to the cationic or anionic species in the pH range of 4.5 to 7.0. There was no influence of ionic strength on the rate of degradation. Arrhenius plots of the data indicated that a shelf life of 2 years or more at room temperature may be obtained in an aqueous solution at a pH value of 6.0.

Development of two stable oral suspensions for gabapentin. Nahata MC. College of Pharmacy, Ohio State University, Columbus 43210, USA.

Abstract Gabapentin is not available in a liquid dosage form for clinical use. This study was designed to develop two oral gabapentin suspensions and determine their stability under refrigeration or at room temperature. Commercially available Gabapentin capsules were used to prepare two suspensions: one in extemporaneously prepared 1% methyl cellulose in syrup (1:1) and another in equal volumes of Commercially available suspending agents/syrup (Ora Plus/Ora Sweet). Each suspension containing gabapentin (100 mg/mL) was stored in 10 plastic prescription bottles; Five were stored at 4 degrees C and five at 25 degrees C. Three 500-microL samples were collected immediately after preparation (day 0) and on days 7, 14, 28, 42, 56, 70, and 91. Gabapentin was measured by accurate, reproducible, specific, and stability-indicating high-performance liquid chromatography (n = 15). The observed mean concentrations exceeded 90% of the initial concentrations in both suspensions for 91 days at 4 degrees C and 56 days at 25 degrees C. No change in pH, odor, or physical appearance was observed. On the basis of these results, stable oral suspensions of gabapentin can be prepared and stored in plastic prescription bottles for 91 days at 4 degrees C or 56 days at 25 degrees C.

Conclusion on Stability The published results are not unified. For a magistal preparation we preferably give a retention period of 2 months. Considering the literature might be best to recommend a storage in the fridge? Recommendation on the ointment base used The buffered Cetomacrogol cream of the TMF has the good pH value for the stability of gabapentin. Presumably, this preparation is prescribed for the treatment of neuropathic pain. If we take into account the bad partition coefficient of gabapentin then the PLO base, which can be purchased from Bassron either in the form of the various components or fully prepared, is highly recommendable. Purchases of the various components are preferable here because we can thus set the pH of the water phase with a buffer. This base seems to be the ideal basis for transdermal absorption, especially for a molecule with a low lipophilic character. Only downside: It excludes the intervention of the RIZIV. The preparation will have to be based on capsules as the raw material is not available in Belgium.