ChemInform Abstract: Interactions and Incompatibilities of Pharmaceutical Excipients with Active Pharmaceutical Ingredients

Bharate, Sonali S.; Bharate, Sandip B.; Bajaj, Amrita

doi:10.1002/chin.201147271

Cited by 120 publications

(159 citation statements)

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“…Incompatibility of hydrocortisone with magnesium stearate is probably due to interaction of the -OH group of hydrocortisone with the bridging carboxylic group of magnesium stearate via hydrogen bonding involving water, similarly as in the case of captopril and magnesium stearate. The literature data show that there are numerous reports on incompatibility of stearates with active pharmaceutical ingredients [6].…”

Section: Pca and Ca As Supporting Techniquesmentioning

confidence: 99%

“…Chemical interactions result in reduction of API quantity in the formulation that can lower its absorption and therapeutic effect. Physical interactions can alter physicochemical properties of the active ingredient, such as solubility, dissolution rate and finally bioavailability [5,6]. There is no universally accepted protocol in the literature or issued by regulatory agencies for evaluating API-excipient compatibility or interactions [7,8].…”

Section: Introductionmentioning

confidence: 99%

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Compatibility studies of hydrocortisone with excipients using thermogravimetric analysis supported by multivariate statistical analysis

Rojek

Wesołowski

2016

J Therm Anal Calorim

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Application of thermogravimetry (TG) alone to study compatibility/incompatibility of active pharmaceutical ingredients (APIs) with excipients yields to misleading results due to overlapping of the thermal stages in the course of decomposition of both ingredients and their pharmaceutical mixtures. Hence, the purpose of this study was to assess the usefulness of multivariate statistical analysis as a supporting tool for interpretation of the TG traces during assessing compatibility of hydrocortisone as an API with selected excipients (mannitol, starch, lactose, methylcellulose, b-cyclodextrin, meglumine, chitosan, magnesium stearate and polyvinylpyrrolidone). The results show that two multivariate techniques, principal component analysis (PCA) and cluster analysis (CA), can be successfully used for interpretation of TG traces, while the TG is used alone as a screening technique to assess compatibility. The results obtained by using TG analysis, supported by PCA and CA, were approved by those of differential scanning calorimetry, infrared spectroscopy and X-ray powder diffraction. Incompatibilities were only found in mixtures of hydrocortisone with magnesium stearate and b-cyclodextrin.

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Section: Pca and Ca As Supporting Techniquesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Compatibility studies of hydrocortisone with excipients using thermogravimetric analysis supported by multivariate statistical analysis

Rojek

Wesołowski

2016

J Therm Anal Calorim

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“…This suggests a possible interaction between simvastatin and lactose. The use of lactose as an excipient for direct compression can sometimes result in drug -excipient incompatibility, as observed in the Maillard reaction (Bharate, Bharate, Bajaj, 2010). Apart from the lactose factor, greater croscarmellose sodium in the formulation was observed, which also contributed to the disintegration of the tablet and release of the active ingredient.…”

Section: Tablet Production and Characterizationmentioning

confidence: 99%

Rational use of antioxidants in solid oral pharmaceutical preparations

Celestino

Magalhães

Fraga

et al. 2012

Braz. J. Pharm. Sci.

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Antioxidants are currently used as efficient excipients that delay or inhibit the oxidation process of molecules. Excipients are often associated with adverse reactions. Stability studies can guide the search for solutions that minimize or delay the processes of degradation. The ability to predict oxidation reactions in different drugs is important. Methods: This study was conducted to assess the rational use of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfite (SMB), propyl gallate (PG) and cysteine (CYS) in tablet formulations of simvastatin and ketoconazole. These antioxidants were evaluated according to stability parameters and the relationship between efficiency of the antioxidant and chemical structure of the drugs. Results were compared with DPPH tests and computational simulations. BHT was most efficient regarding simvastatin stability, and the most effective BHT concentrations for maintaining stability were 0.5 and 0.1%. In relation to ketoconazole, SMB was most efficient for maintaining content and dissolution profile. The evaluation by DPPH showed that the largest percentage of absorbance reduction was observed for PG, while SMB proved most efficient and had lower consumption of DPPH. The same pattern was observed, albeit with lower efficiency, for the other lipophilic antioxidants such as BHT and BHA. The results of the molecular modeling study demonstrated that electronic properties obtained were correlated with antioxidant activity in solution, being useful for the rational development of liquid pharmaceutical formulations but not for solid oral formulations. This study demonstrated the importance of considering stability parameters and molecular modeling to elucidate the chemical phenomena involved in antioxidant activity, being useful for the rational use of antioxidants in the development of pharmaceutical formulations.Uniterms: Antioxidants/rational use. Excipients/evaluation. Butylated hydroxyanisole/rational use. Butylated hydroxytoluene/rational use. Sodium metabisulfite/rational use. Propyl gallate/rational use. Cysteine/rational use. Simvastatin/tablets/evaluation. Ketoconazole/tablets/evaluation. Atualmente, antioxidantes são usados como excipientes eficientes, que retardam ou inibem o processo de oxidação de moléculas. Excipientes são frequentemente associados a efeitos adversos. Estudos de estabilidade podem ajudar na busca por possíveis soluções para minimizar ou retardar os processos de degradação. A habilidade de prever as reações de oxidação em diferentes fármacos é importante. O estudo foi conduzido com o objetivo de avaliar o uso racional de hidroxianisol butilado (BHA), hidroxitolueno butilado (BHT), metabissulfito sódico (SMB), galato de propila (PG) e cisteína (CYS) em formulações de comprimidos de sinvastatina e cetoconazol. Eles foram avaliados por parâmetros de estabilidade e pela relação entre a eficiência dos antioxidantes e a estrutura química do fármaco. Os resultados foram comparados com testes de DPPH e simulações em computador. BHT f...

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“…Additionally, lactose has a degree of security as inert excipient due to its incompatibility with compounds that have primary amine moieties (e.g. budesonide and formoterol), since Maillard-type condensation reaction is likely to occur (Bharate et al, 2010). Furthermore, although the side effects of lactose intolerance will sometimes not be observed in a patient using the small amounts of lactose present in tablets, the NOCEBO-effect should not be ignored.…”

Section: Introductionmentioning

confidence: 99%

Influence of mannitol concentration on the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol

Kaialy

Mawlud

2016

International Journal of Pharmaceutics

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Mannitol is a pharmaceutical excipient that is receiving increased popularity in solid dosage forms. The aim of this study was to provide comparative evaluation on the effect of mannitol concentration on the physicochemical, mechanical, and pharmaceutical properties of lyophilised mannitol. The results showed that the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol powders are strong functions of mannitol concentration. By decreasing mannitol concentration, the true density, bulk density, cohesivity, flowability, netcharge-to-mass ratio, and relative degree of crystallinity of LM were decreased, whereas the breakability, size distribution, and size homogeneity of lyophilised mannitol particles were increased. The mechanical properties of lyophilised mannitol tablets improved with decreasing mannitol concentration. The use of lyophilised mannitol has profoundly improved the dissolution rate of indomethacin from tablets in comparison to commercial mannitol. This improvement exhibited an increasing trend with decreasing mannitol concentration. In conclusion, mannitols lyophilised from lower concentrations are more desirable in tableting than mannitols from higher concentrations due to their better mechanical and dissolution properties. Abbreviations∆H0, Endothermic enthalpy of CM melting; ∆Hs, Endothermic enthalpy of LM melting; ANOVA, One-way analysis of variance; API, Active pharmaceutical ingredient; c.opt, Optimal concentration; CI, Carr's index; CM, Commercial mannitol; Cman, Concentration of mannitol; d10%, particle size at 10% volume distribution; d50%, particle size at 50% volume distribution; d90%, particle size at 90% volume distribution; Db, Bulk density, DE, Dissolution efficiency; DSC, Differential scanning calorimeter; Dt, tap density; EB, Ease of breakage; Eq, Equation; FT-IR, Fourier transform infrared; GI, Gastro intestinal; HSD, Honestly Significant Difference; I, Relative intensity; Iamorphous, the input to the intensity from the amorphous region; Icrystalline, the input to the intensity from the crystalline region; LM, Lyophilised mannitol; MDR, Mean dissolution rate; MDT, Mean dissolution time; P, Statistical probability; PXRD, Powder X-ray diffraction; Q10min, The mean percentage of drug dissolved in the first 10 min; Q30min, The mean percentage of drug dissolved in the first 30 min; Q4min, The mean percentage of drug dissolved in the first 4 min; Q50min; The mean percentage of drug dissolved in the first 50 min; RDB, Relative degree of breakage;

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ChemInform Abstract: Interactions and Incompatibilities of Pharmaceutical Excipients with Active Pharmaceutical Ingredients

Abstract: Review: 130 refs.

Cited by 120 publications

References 0 publications

Compatibility studies of hydrocortisone with excipients using thermogravimetric analysis supported by multivariate statistical analysis

Compatibility studies of hydrocortisone with excipients using thermogravimetric analysis supported by multivariate statistical analysis

Rational use of antioxidants in solid oral pharmaceutical preparations

Influence of mannitol concentration on the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol

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