Chemical reactivity in solid-state pharmaceuticals: formulation implications

Byrn, Stephen R.; Xu, Wei; Newman, Ann

doi:10.1016/s0169-409x(01)00102-8

Cited by 233 publications

(157 citation statements)

References 34 publications

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“…This is to be expected as water has a direct role in the transesterification reaction, but reduction in degradation rate can also be due to a loss of molecular mobility induced by the solid state. [26][27][28] However, if that is well established for pharmaceuticals, there is no direct evidence for nucleic acids.…”

Section: Discussionmentioning

confidence: 99%

An efficient method for long-term room temperature storage of RNA

Fabre

Colotte²,

Luis³

et al. 2013

Eur J Hum Genet

113

110

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RNA is a tool used in many fields, from molecular and cellular biology to medicine and nanotechnology. For most of these uses, the integrity of RNA is required and must be maintained during storage. Even though freezing is currently the storage method of choice, the increasing number of samples to be stored and the costly use of a cold chain have highlighted the need for room temperature preservation methods. Here, we report a new room temperature technology that consists in drying RNA samples in the presence of a stabilizer in stainless steel minicapsules. These air-and water-tight capsules isolate RNA from the atmosphere and maintain an anhydrous and anoxic environment. Through the evaluation of RNA integrity over time at room temperature or 90 1C, we identified atmospheric humidity as a major deleterious factor. The degradation rate dependence in temperature fitted an Arrhenius model, with an activation energy of 28.5 kcal/mol and an extrapolated room temperature degradation rate of 3.2 10 À13 /nt/s (95% confidence interval: 2.3-4.2/nt/s). In these conditions, it is expected that an RNA molecule will be subjected to 0.7-1.3 cut every 1000 nucleotides per century. In addition, we showed that stored RNA is compatible for further analyses, such as reverse transcription-quantitative PCR. No significant change in the C q values was observed over a simulated period of several decades. At last, our data are consistent with a sequence-independent degradation rate of RNA in the solid state.

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Section: Discussionmentioning

confidence: 99%

An efficient method for long-term room temperature storage of RNA

Fabre

Colotte²,

Luis³

et al. 2013

Eur J Hum Genet

113

110

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“…This application was expanded to the synthesis of API metal complexes by Braga and co-workers who explored the complexation of zinc, copper(II) and silver(I) with drug molecules such as gabapentin and 4-aminosalicylic acid. 36,74 The solid-state reactivity of metal oxides to yield derivatives of pharmaceuticals was extensively studied and described by Byrn and co-workers 75 who observed the slow reaction of magnesium oxide and non-steroidal anti-inflammatory drug (NSAID) pharmaceuticals upon exposure of solid-state mixtures to moisture at room temperature. We have explored the same type of oxidebased reactivity in the mechanochemical environment, by liquid-assisted grinding together of MgO with NSAIDs ibuprofen (S-and RS-forms), 76 salicylic acid and naproxen in a 1:2 stoichiometric ratio using water as the grinding liquid (Figure 9a).…”

Section: Pharmaceutical Derivatives and Metallodrugsmentioning

confidence: 99%

Clean and Efficient Synthesis Using Mechanochemistry: Coordination Polymers, Metal-Organic Frameworks and Metallodrugs

Friščić¹,

Halász²,

Štrukil³

et al. 2012

Croat. Chem. Acta

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Abstract. This review briefly discusses recent advances and future prospects in the mechanochemical synthesis of coordination compounds by ball milling and grinding, and highlights our contributions to the mechanosynthesis of porous metal-organic frameworks (MOFs) and zeolitic imidazolate frameworks (ZIFs), metal-organic pharmaceutical derivatives and metallodrugs using the recently developed mechanochemical methods of liquid-assisted grinding (LAG) and ion-and liquid-assisted grinding (ILAG). The role of mechanochemistry in the development of a solvent-free laboratory, cocrystal synthesis and new materials for luminescence and gas absorption is also highlighted. (doi: 10.5562/cca2014)

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“…Differential scanning calorimeter (DSC) allows the fast evaluation of possible incompatibilities because it shows changes in the appearance, shift or disappearance of melting endotherms and exotherms and variations in the corresponding enthalpies of reaction. [24] The DSC thermograms of pure drug and coated tablets were recorded. The samples were separately sealed in aluminum cells and set in Perkin Elmer (Pyris 1) DSC (Waltham, MA).…”

Section: Drug-excipient Interaction Studiesmentioning

confidence: 99%

Untitled

Kumaravelrajan¹

2016

AJP

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Introduction: A system that can deliver multidrugs at a controlled rate is very important to the treatment of various chronic diseases such as diabetes, asthma, and hypertension. In general, both highly and poorly water-soluble drugs are not good candidates for elementary osmotic delivery, so in the present investigation nifedipine-hydroxyproyl-β-cyclodextrin (1:1) inclusion complex was used to modulate the solubility of nifedipine (NP) within the core and metoprolol was used not only as the active ingredient but also as osmotic agent. Materials and Methods: NP-cyclodextrin complex was prepared by coprecipitation method. The tablets were prepared and coated with cellulose acetate phthalate-containing dibutyl phthalate as plasticizer at various concentrations. The coated tablets drilled for orifice. The orifice size, level of plasticizer, and coating thickness were used as formulation variables. Finally, the optimized formulation was studied for different pH, agitational speed, and release mechanism. The optimized formulation was also subjected to in vivo prediction for the desired C max and C min using superposition method. Results: Formulation variables such as orifice size, level of plasticizer, and coat thickness of semipermeable membrane were found to affect the drug release from the developed formulations. The optimal elementary osmotic pump was found to deliver both drugs at a rate of approximately zero order for up to 10 h independent of pH and agitational intensity but dependent on the osmotic pressure of the release media. Conclusion: Hence, the prototype design of the system could be applied to other combinations of drugs used for cardiovascular diseases, diabetes, etc.

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Chemical reactivity in solid-state pharmaceuticals: formulation implications

Cited by 233 publications

References 34 publications

An efficient method for long-term room temperature storage of RNA

An efficient method for long-term room temperature storage of RNA

Clean and Efficient Synthesis Using Mechanochemistry: Coordination Polymers, Metal-Organic Frameworks and Metallodrugs

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