Solid State Stability and Preformulation Studies for Acetylcholinesterase Inhibitor Drug Tacrine

In this paper, the acetylcholinesterase inhibitor drug tacrine was investigated by two complementary instrumental techniques, namely infrared spectroscopy and thermal analysis, as pure drug and in solid binary mixtures with nine excipients frequently used in the pharmaceutical industry, namely starch, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30, fumed silica (Aerosil), talc, anhydrous lactose, magnesium stearate, mannitol and calcium lactate pentahydrate. The corroboration of obtained data by the two complementary methods confirmed the incompatibility of this drug with anhydrous lactose, mannitol, magnesium stearate and calcium lactate under both ambient conditions and thermal stress, and thermally induced interactions between tacrine and silica. In the development of new generic solid formulations, four of the investigated excipients (i.e., starch, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30 and talc) can be used, since they are compatible with tacrine under ambient conditions as well as under thermal stress.

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Stability and Compatibility Studies of Levothyroxine Sodium in Solid Binary Systems—Instrumental Screening

Pharmaceutics ◽

10.3390/pharmaceutics12010058 ◽

2020 ◽

Vol 12 (1) ◽

pp. 58 ◽

Cited By ~ 1

Author(s):

Ionuț Ledeți ◽

Mirabela Romanescu ◽

Denisa Cîrcioban ◽

Adriana Ledeți ◽

Gabriela Vlase ◽

...

Keyword(s):

Thermal Stress ◽

Binary Systems ◽

Therapeutic Index ◽

Magnesium Stearate ◽

Hydroxyethyl Cellulose ◽

Attenuated Total Reflectance ◽

Ambient Conditions ◽

Narrow Therapeutic Index ◽

The Stability ◽

Anhydrous Lactose

The influence of excipients on the stability of sodium levothyroxine pentahydrate (LTSS) under ambient conditions and thermal stress was evaluated. Since LTSS is a synthetic hormone with a narrow therapeutic index, the interactions of LTSS with excipients can lead to a drastic diminution of therapeutic activity. Ten commonly used pharmaceutical excipients with different roles in solid formulations were chosen as components for binary mixtures containing LTSS, namely, starch, anhydrous lactose, D-mannitol, D-sorbitol, gelatin, calcium lactate pentahydrate, magnesium stearate, methyl 2-hydroxyethyl cellulose (Tylose), colloidal SiO2 (Aerosil) and talc. As investigational tools, universal attenuated total reflectance- Fourier transform infrared spectroscopy UATR-FTIR spectroscopy and thermal analysis were chosen and used as follows: UATR-FTIR spectra were drawn up for samples kept under ambient conditions, while thermoanalytical tools (TG/DTG/HF data) were chosen to evaluate the inducing of interactions during thermal stress. The corroboration of instrumental results led to the conclusion that LTSS is incompatible with lactose, mannitol and sorbitol, and these excipients should not be considered in the development of new generic solid formulations.

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Risperidone/Randomly Methylated β-Cyclodextrin Inclusion Complex—Compatibility Study with Pharmaceutical Excipients

Molecules ◽

10.3390/molecules26061690 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1690

Author(s):

Laura Sbârcea ◽

Ionuț-Mihai Tănase ◽

Adriana Ledeți ◽

Denisa Cîrcioban ◽

Gabriela Vlase ◽

...

Keyword(s):

Inclusion Complex ◽

Uv Spectroscopy ◽

Magnesium Stearate ◽

Phase Solubility ◽

Compatibility Study ◽

Spectroscopic Techniques ◽

Ambient Conditions ◽

Pharmaceutical Excipients ◽

Supramolecular Adduct ◽

Anhydrous Lactose

Risperidone (RSP) is an atypical antipsychotic drug used in treating schizophrenia, behavioral, and psychological symptoms of dementia and irritability associated with autism. The drug substance is practically insoluble in water and exhibits high lipophilicity. It also presents incompatibilities with pharmaceutical excipients such as magnesium stearate, lactose, and cellulose microcrystalline. RSP encapsulation by randomly methylated β-cyclodextrin (RM-β-CD) was performed in order to enhance drug solubility and stability and improve its biopharmaceutical profile. The inclusion complex formation was evaluated using thermal methods, powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy, and saturation solubility studies. The 1:1 stoichiometry ratio and the apparent stability constant of the inclusion complex were determined by means of the phase solubility method. The compatibility between the supramolecular adduct and pharmaceutical excipients starch, anhydrous lactose, magnesium stearate, and cellulose microcrystalline was studied employing thermoanalytical tools (TG-thermogravimetry/DTG-derivative thermogravimetry/HF-heat flow) and spectroscopic techniques (UATR-FTIR, PXRD). The compatibility study reveals that there are no interactions between the supramolecular adduct with starch, magnesium stearate, and cellulose microcrystalline, while incompatibility with anhydrous lactose is observed even under ambient conditions. The supramolecular adduct of RSP with RM-β-CD represents a valuable candidate for further research in developing new formulations with enhanced bioavailability and stability, and the results of this study allow a pertinent selection of three excipients that can be incorporated in solid dosage forms.

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