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Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Joseph M. Caster, Artish N. Patel, Tian Zhang, Andrew Wang
Saint Stephens Aids Trust and the University of Liverpool are investigating polymeric nanoformulations of two antiretroviral agents used for HIV treatment. Efavirenz is a non-nucleoside reverse transcriptase inhibitor clinically used as the preferred first line treatment for HIV infection [70]. Lopinavir is a protease inhibitor commonly utilized in combination therapy. Nano-formulations of these antiretroviral agents aim to reduce total dosage and cost in order to improve patient tolerability while maintaining clinical efficacy. Preclinical studies have demonstrated bioequivalent efficacy in suppressing HIV-1 replication and slower emergence of drug resistance with HIV-IIIB and subtype A virus. Development of NANOEfavirenz and NANOLopinavir has reached phase I trials examining safety and tolerability in HIV negative, healthy patients as well as the bioequivalence of these nanoformulations to the free drugs Sustiva (Efavirenz) and Kaletra (Lopinavir/Ritonavir). Results have yet to be published.
Pharmaceutical Applications of Carrageenan
Published in Amit Kumar Nayak, Md Saquib Hasnain, Dilipkumar Pal, Natural Polymers for Pharmaceutical Applications, 2019
A. Papagiannopoulos, S. Pispas
Carrageenan possesses anti-HIV activity as it inhibits entry and attachment of the virus (Woodsong and Holt, 2015) and has been the basis of carraguard. It is one of a series of polymers considered as mucoadhesive materials while it particularly prevents infection by binding to the virus surface, stopping microbes from adhering to cells (Valenta, 2005). The polysaccharide has also been involved in carrier gels (Singer et al., 2011) for non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150. Carrageenan gels were shown to be safe (Skoler-Karpoff et al.), and their physicochemical properties render them promising for the delivery of anti-HIV active pharmaceutical ingredients (APIs) (Fernández-Romero et al., 2007, 2012). Additionally, carrageenan has been applied in microbicides with antiviral activity (Maguire et al., 1998) and animal models against HPV (Roberts et al., 2011). Acetate-carrageenan is under investigation for possible activity against HSV and HPV (Levendosky et al., 2015).
Examples from the Chemical Industry
Published in John Andraos, Synthesis Green Metrics, 2018
Efavirenz is a non-nucleoside reverse transcriptase inhibitor developed by Merck as a treatment for HIV-1 (human immunodeficiency virus type 1). A medicinal chemistry discovery route (G1) and two process chemistry routes (G2 and G3) are shown below. All three routes begin from the same starting material, 1-(2-amino-5-chloro-phenyl)-2,2,2-trifluoro-ethanone. Merck claimed that the material efficiency for the synthesis of this pharmaceutical improved progressively from G1 to G3. The key challenge in the synthesis of this compound is the generation of the stereogenic quaternary center. The medicinal chemistry route makes the racemic compound which is then resolved using a diastereomeric discriminant. The process routes use a norephedrine analog as a chiral auxiliary.
Green HPLC quantification method of lamivudine, zidovudine and nevirapine with identification of related substances in tablets
Published in Green Chemistry Letters and Reviews, 2022
Ludivine Vieira-Sellaï, Mercedes Quintana, Ousmane Diop, Olivier Mercier, Sebastien Tarrit, Nawal Raimi, Alassan Ba, Benoit Maunit, Marie-Josephe Galmier
Antiretroviral drugs, like the Nucleoside Reverse Transcriptase Inhibitors (NRTIs) lamivudine (3TC) and zidovudine (AZT) and the non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) nevirapine (NVP) (Figure 1) are widely prescribed to treat HIV infections in resource-limited countries. A fixed-dose combination of these three drugs appeared in 2005 (1) and now it is included in the WHO’s list of essential medicines (2) and is available in adult and pediatric doses. A number of HPLC quantification methods of 3TC, AZT and NVP in pharmaceutical forms for performing pharmaceutical control analysis and combating the emergence of counterfeit medicines can be found in the literature (3–6) as well as in the official HPLC methods in pharmacopoeias. The European, United States (USP) and international (Ph. Int.) pharmacopoeias contain single monographs for each active principal ingredient (API). The USP and Ph. Int. also integrate the monographs for pharmaceutical products and the simultaneous dosage of 3TC, AZT and NVP in tablets is only available in Ph. Int. (7). These methods used acetonitrile (ACN) or methanol (MeOH), the most widely used solvents in RP-HPLC and acetate or phosphate buffer as mobile phases. However, methanol and ACN solvents are included on the EPA hazardous waste (8) and on ICH Q3C guideline (R8) (9). They should be properly disposed or recycled because discharging untreated wastewater containing ACN into natural water systems can cause serious ecological environmental damage. Minimizing ACN or MeOH consumption in analytical scientific process is therefore crucial in increasing the sustainability of pharmaceutical analysis (10, 11), and even more so in resource-limited countries where waste management and treatment constitutes a serious problem (12). At present, Eco-Friendly methods are developed using several chromatographic methods and types of pharmaceutical drugs (11, 13–16). To best of our knowledge, to date no green HPLC method has been proposed for determining 3TC, AZT or NVP in pharmaceutical forms, whether separately or simultaneously. The objective of the present work was to develop a green HPLC method for the simultaneous analysis of 3TC, AZT and NVP and its application in tablets for both paediatric and adult patients with the ethanol integration as a mobile phase. Additionally, the method was adapted to complete the analysis of five related substances described in the Ph. Int., five other known related substances and two excipients (Figure 2). For that, ethanol (a biodegradable solvent, less toxic than ACN and MeOH) was successfully incorporated as the organic mobile phase using a typical HPLC pump (< 400 bar pressure). At the same time, the column diameter reduction (3 mm instead of 4.6 mm as used in Pharmacopoeias) was used to minimize waste generation and, therefore, waste management. Sample processing was also optimized using ethanol as a solvent, with the minimization of standard quantities and volume solutions. The proposed method should be easily implemented in quality control laboratories and in particular in the laboratories of resource-limited countries.