Pharmaceutical applications of citric acid

Nangare, Sopan; Vispute, Yogini; Tade, Rahul; Dugam, Shailesh; Patil, Pravin

doi:10.1186/s43094-021-00203-9

Future Journal of Pharmaceutical Sciences

Table 1 Summary of pharmaceutical applications of CA

From: Pharmaceutical applications of citric acid

Sr. No	Application of CA	Active agent	Composite	Result/Inference	Ref.
1.	Green crosslinker	CIFLOX	PVA-CA-AgNPs	1. CA acted as a green crosslinker of PVA by esterification reaction. 2. The number of free carboxyl groups in CA provided pH sensitivity and antimicrobial properties to the PVA.	[14]
2.	Green crosslinker	–	PVA-CA	1. Aqueous stability plus biocompatibility of PVA increased.	[15]
3.	Green crosslinker	Fe₂O₃	Fe₂O₃-CA-MNPs	1. It shows good superparamagnetic behavior. 2. It increased the antibacterial activity of Fe₂O_3.	[16]
4.	Green crosslinker	Ketoconazole	β-CD-HEC-CA	1. It provides the controlled release of ketoconazole.	[17]
5.	Green crosslinker	Diclofenac sodium	CL-MPH	1. It shows the stimuli-responsive zero-order release of the drug.	[18]
6.	Green crosslinker	–	CA-WPI	1. It confirmed that the CA is a novel gelling agent.	[19]
7.	Green crosslinker	–	WPI-CA	1. The crosslinking of WPI-CA increased the overall gel water holding capacity 2. CA interlinking resulted in a much more digestibility decrease than swelling.	[21]
8.	Green crosslinker	–	WPI-CA	1. It resulted in higher water-holding capacity plus denser microstructure.	[22]
9.	Green crosslinker	MB, Tetracycline	NaCMC-HPMC	1. It provides the sustained release of the drug (up to 72 h). 2. It demonstrated significant antibacterial activity.	[11]
10.	Green crosslinker	–	Xanthan-CA hydrogel	1. The cross-linking decreases the swelling of the hydrogels whereas improving their structure to stabilize the products when submerged in water.	[23]
11.	Green crosslinker	Tramadol	PEGD: CA/GEL	1. It provides the low-cost 3D hydrogel with an anomalous drug transport mechanism for the release of tramadol.	[23]
12.	Green crosslinker	MB	CMC-PEO	1. It provides the pH-dependent release of MB.	[24]
13.	Green crosslinker	Ketoconazole	CMC-PEG hydrogel	1. It provides the controlled release of ketoconazole.	[17]
14.	Green crosslinker	Moxifloxacin hydrochloride	CMTG-CA	1. Prepared biocompatible hydrogel provides the controlled release of drugs along with a non-Fickian drug transport mechanism.	[25]
15.	Green crosslinker	Levofloxacin	Starch-CA	1. The reduced level of matrix hydration resulted in a long-time release of levofloxacin.	[26]
16.	Green crosslinker	Cefixime	CA-Ag-Gelatine	1. It demonstrates the pH-dependent swelling of hydrogel and release of the drug.	[27]
17.	Co-crystal	Effervescent product	CA-NIC	1. CA improves eeffervescent product stability.	[28]
18.	pH modifier	SBA-1	SBA-15CTA	1. It confirmed that the CA containing two carboxyl groups is more effective for the development of high-quality SBA.	[29]
19.	pH modifier	AZA	AZA@CA	1. The inclusion of CA increased the basic amino group’s ionization in AZA. 2. It increased its release in dissolution colonic pH.	[30]
20.	Fluorescent material	–	TPCA	1. It provides strong fluorescence. 2. It shows the selectivity toward interest analyte.	[30]
21.	Fluorescent material	siRNA	PPFR	1. PPFR exhibited stable photoluminescent aptitude. 2. It successfully binds and guards the siRNA against RNase.	[31]
22.	Fluorescent material	–	CA-GQDs	1. It synthesized stable blue luminescent GQDs.	[32]
23.	Fluorescent material	DOX	CA-CDs-DOX	1. It shows the higher cellular uptake plus good anti-tumor potential	[33]
24.	Capping agent	Quercetin	CA/α-CD-IONPs	1. It provides the stable IONPs 2. It shows the pH-dependent release of quercetin.	[34]
25.	Capping agent	Zn₀.₃Fe₂.₇O₄ NPs	PEG- Zn₀.₃Fe₂.₇O₄ NPs	1. It gives non-toxic and stable nanoparticles.	[35]
26.	Coating agent	CA-CoFe₂O₄-NPs	CA-CoFe₂O₄-NPs	1. It gives the stable and biocompatible NPs.	[36]
27.	Dendrimers	CFTX	Peg-CA-CFTX	1. It provides sustained release (48 h) and good antibacterial activity against Gram-negative and Gram-positive bacteria.	[37]
28.	Dendrimers	Econazole	Econazole-CA- dendrimers	1. It shows excellent antifungal activity.	[38]
29.	Dendrimers	AuNPs	CA- dendrimers	1. It synthesized the CA-based dendrimers gives stable and uniform AgNPs.	[40]
30.	Dendrimers	Naproxen	CA-PEG-CA	1. It provides the high loading of naproxen followed by increasing the release of naproxen.	[40]
31.	Polymeric conjugates	5-FU	FA-TGA AuNPs	1. It provides the targeted and sustained drug release of 5-FU. 2. FA-TGA AuNPs nanoconjugates increased the cell proliferation of normal cells without toxicity.	[41]
32.	Polymeric conjugates	–	GO-g-PCA/Fe₃O₄@ZnO	1. It improved the overall photocatalytic activity of nanocomposite.	[42]
33.	Polymeric conjugates	Cy5-dye (as a model)	PG-CA-NPs	1. It shows a higher cellular uptake and good biocompatibility.	[43]
34.	Polymeric conjugates	–	CPHP	1. It develops the water-soluble polymeric conjugates. 2. It gives more than 80% cell viability.	[44]
35.	Hyperbranched polymer	Cisplatin	CA–glycerol	1. It shows the high loading of cisplatin and efficient delivery of the same. 2. It shows a lower IC50 value than the pure anticancer drug, which confirmed the biocompatibility of copolymers.	[45]
36.	Solvent	Amoxicillin	Pectin	1. It helps to synthesize the pectin with low degree esterification. 2. Owing to low degree esterification, it shows good gelling ability and subsequently retard the release of the drug.	[46]
37.	Superdisnitegrant	Paracetamol	Citrated taro starch	1. It reduces the disintegration time of tablets. 2. It enhances the dissolution efficiency of the tablet.	[47]
38.	Gas generating agent	Quinapril hydrochloride	–	1. It shows a good floating profile. 2. It gives the sustained release of the drug for 12 h.	[48]
39.	Gas generating agent	Tapentadol hydrochloride	–	1. It exhibited the good floating profile 2. It provides the controlled release of tapentadol hydrochloride.	[49]
40.	Release enhancer	Ranitidine hydrochloride	–	1. The less concentration of CA and high concentration of stearic acid resulted in sustained release of ranitidine. 2. The addition of CA into dosage form enhanced the release rate of the drug.	[50]
41.	Stabilizer	–	Zn_xFe_3-xO₄ NPs	1. CA offers stable, size-controlled, crystalline nanoparticles. 2. CA plays an important role as a reducing agent and modulation in the development of spinel structure.	[51]
42.	Absorption enhancer	Glucagon	Glucagon-DPI	1. It increased the absorption of glucagon in DPI. 2. It improved the dissolution of glucagon in the targeted side.	[52]

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