Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations

Gupta, Divender; Bhatia, Deepak; Dave, Vivek S; Sutariya, Vijaykumar; Gupta, Sheeba Varghese

doi:10.3390/molecules23071719

Cited by 161 publications

(102 citation statements)

References 49 publications

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“…Regarding the API-loaded BNC membranes, the moisture-uptake is dependent on the API nature with lidocaine and diclofenac exhibiting the highest moisture-uptake values particularly at higher RH and temperature, namely, 19.8 ± 4.1% at 60% RH/25 • C and 36.3 ± 2.1% at 75% RH/40 • C for BNC/lidocaine, and 9.2 ± 1.0% at 60% RH/25 • C and 31.3 ± 7.3% at 75% RH/40 • C for BNC/diclofenac ( Table 2). These data are clearly related with the fact that the former is in the hydrochloride hydrate form, while the latter is in the sodium salt form, which on the whole leads to higher hygroscopicity of the former, as discussed elsewhere [44]. On the other hand, the caffeine-loaded BNC membrane presents a lower moisture-uptake with values of 16.5 ± 0.7% at 60% RH/25 • C and 26.0 ± 4.5% at 75% RH/40 • C, whereas the ibuprofen-loaded BNC membrane exhibits the lowest moisture-uptake values, i.e., 4.1 ± 1.4% at 60% RH/25 • C and 12.3 ± 2.9% at 75% RH/40 • C (Table 2), due to the hydrophobic character of the drug.…”

Section: Storage Stability Studies Of the Api-loaded Bnc Membranessupporting

confidence: 59%

Topical Drug Delivery Systems Based on Bacterial Nanocellulose: Accelerated Stability Testing

Silva

Mota

Almeida

et al. 2020

IJMS

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Bacterial nanocellulose (BNC) membranes have enormous potential as systems for topical drug delivery due to their intrinsic biocompatibility and three-dimensional nanoporous structure, which can house all kinds of active pharmaceutical ingredients (APIs). Thus, the present study investigated the long-term storage stability of BNC membranes loaded with both hydrophilic and lipophilic APIs, namely, caffeine, lidocaine, ibuprofen and diclofenac. The storage stability was evaluated under accelerated testing conditions at different temperatures and relative humidity (RH), i.e., 75% RH/40 °C, 60% RH/25 °C and 0% RH/40 °C. All systems were quite stable under these storage conditions with no significant structural and morphological changes or variations in the drug release profile. The only difference observed was in the moisture-uptake, which increased with RH due to the hydrophilic nature of BNC. Furthermore, the caffeine-loaded BNC membrane was selected for in vivo cutaneous compatibility studies, where patches were applied in the volar forearm of twenty volunteers for 24 h. The cutaneous responses were assessed by non-invasive measurements and the tests revealed good compatibility for caffeine-loaded BNC membranes. These results highlight the good storage stability of the API-loaded BNC membranes and their cutaneous compatibility, which confirms the real potential of these dermal delivery systems.

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Section: Storage Stability Studies Of the Api-loaded Bnc Membranessupporting

confidence: 59%

Topical Drug Delivery Systems Based on Bacterial Nanocellulose: Accelerated Stability Testing

Silva

Mota

Almeida

et al. 2020

IJMS

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“…Amino acids as salt formers also impact the membrane permeability of the resultant salts and thereby affect their overall efficacy. Salt formation often increases the stability and alters lipophilicity of the drug and hence eases the drug permeation across the lipophilic cellular barriers [169]. However, amino acids can be used to improve membrane permeability of drugs by increasing their hydrophilicity via salt formation.…”

Section: Amino Acids As Solubility Enhancing Agentsmentioning

confidence: 99%

Multimodal Role of Amino Acids in Microbial Control and Drug Development

et al. 2020

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Amino acids are ubiquitous vital biomolecules found in all kinds of living organisms including those in the microbial world. They are utilised as nutrients and control many biological functions in microorganisms such as cell division, cell wall formation, cell growth and metabolism, intermicrobial communication (quorum sensing), and microbial-host interactions. Amino acids in the form of enzymes also play a key role in enabling microbes to resist antimicrobial drugs. Antimicrobial resistance (AMR) and microbial biofilms are posing a great threat to the world’s human and animal population and are of prime concern to scientists and medical professionals. Although amino acids play an important role in the development of microbial resistance, they also offer a solution to the very same problem i.e., amino acids have been used to develop antimicrobial peptides as they are highly effective and less prone to microbial resistance. Other important applications of amino acids include their role as anti-biofilm agents, drug excipients, drug solubility enhancers, and drug adjuvants. This review aims to explore the emerging paradigm of amino acids as potential therapeutic moieties.

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“…There are proposed changes in Canada where a declaration of equivalence could be given to a subsequent-entry IV product that is a different salt form of the medicinal ingredient as long as the therapeutically active component is chemically identical to the reference product (14,15). However, a recent review highlights the impact that a chosen salt form can have on the physiochemical and biological properties of the active pharmaceutical ingredients (41). In this regard, the salt form chosen can impact the drug's polymorphism, solubility, particle size, stability of formulation, as well as other criteria that have an effect on the physiochemical properties which can influence the release of the product.…”

Section: Relevant Canadian Guidancementioning

confidence: 99%

Need for Bioequivalence Standards that Reflect the Clinical Importance of the Complex Pharmacokinetics of Paliperidone Palmitate Long-Acting Injectable Suspension

Procyshyn

Lamoure²,

Katzman

et al. 2019

J Pharm Pharm Sci

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Paliperidone palmitate is a second generation antipsychotic, approved for the treatment of schizophrenia in the form of the long-acting injectable (LAI) products INVEGA SUSTENNA® (once monthly injection) and INVEGA TRINZA® (once every 3 months injection). Paliperidone palmitate dissolves slowly after deep intramuscular injection before being hydrolyzed to paliperidone and absorbed into the systemic circulation. The pharmacokinetic (PK) profile of the INVEGA SUSTENNA® formulation is biphasic, comprised of an initial relatively fast zero-order input, which allows rapid attainment of therapeutic concentrations without oral supplementation; and a subsequent maintained second-stage, first-order input, allowing for once monthly administration. Changes to the manufacturing processes can substantially alter the release characteristics of paliperidone palmitate LAI and consequently its PK profile. As an example, larger or smaller particle sizes of paliperidone palmitate can result in a delayed or accelerated release of paliperidone into the systemic circulation, respectively. Such changes are clinically relevant, as transient excursions above therapeutic plasma concentrations can be associated with an increased risk of adverse effects, including tachycardia, hypotension, QT prolongation, and extrapyramidal symptoms. Conversely, a delay in attaining therapeutic plasma concentrations of paliperidone on initiation of treatment, or a return to low plasma concentrations before the end of a dosing interval during repeated dosing, increases the risk of relapse. Given the integral relationship of the PK profile to the product’s clinical effects, it is important to have bioequivalence standards that reflect the complexity of the paliperidone palmitate LAI PK profile if one is to consider therapeutic equivalence based on simple bioequivalence testing. Although both the EMA and U.S. FDA have product-specific guidelines to determine bioequivalence, their requirements differ substantially. In Canada, no LAI product-specific bioequivalence guidance exists for multiphasic medication delivery systems, and the recently revised Comparative Bioavailability Standards: Formulations Used for Systemic Effects guidance applies only to oral and non-injectable formulations. We recommend that new Canadian standards be developed for multiphasic and biphasic intramuscular / subcutaneous (IM/SC) products, including paliperidone palmitate LAI products, because, similar to modified-release oral dosage forms, a different PK profile in modified-release IM/SC products can result in clinically meaningful differences in safety, efficacy, and tolerability. To ensure bioequivalence for both newly initiated and switch patients, this paper proposes bioequivalence standards that could be adopted in Canada that include two studies, a multiple-dose cross-over study, and a single-dose study with partial AUC metrics.

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Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations

Cited by 161 publications

References 49 publications

Topical Drug Delivery Systems Based on Bacterial Nanocellulose: Accelerated Stability Testing

Topical Drug Delivery Systems Based on Bacterial Nanocellulose: Accelerated Stability Testing

Multimodal Role of Amino Acids in Microbial Control and Drug Development

Need for Bioequivalence Standards that Reflect the Clinical Importance of the Complex Pharmacokinetics of Paliperidone Palmitate Long-Acting Injectable Suspension

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