ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF ANTIMICROBIAL FORMULATIONS – A REVIEW

ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF ANTIMICROBIAL FORMULATIONS - A REVIEW

Aditi Tyagi and Hiral Dave *

Department of Pharmaceutical Quality Assurance, Parul Institute of Pharmacy, Parul University, Vadodara, Gujarat, India.

ABSTRACT: Microbes are widespread and have been studied widely in recent years. Disease-causing microbes can also be called pathogens, germs, or bugs. These microbes are responsible for causing infectious diseases. Microbes are mediators in almost all ecosystem processes and act as a global pivotal game changer in various ecological activities. The therapeutic outcome with antimicrobial drugs depends totally on the selection of antimicrobial drugs. The choice of antimicrobial drugs depends on causative agents, patient factors, and clinical pharmacology of antimicrobial agents. The current review discusses how microbes can enter the human body through different sites and how antimicrobial drugs help cure various infectious diseases. Along with the same, the current review also represents how antimicrobial drugs affect the viability of microorganisms. The article also incorporates the prophylactic use of antimicrobial drugs. The main objective of the current review article is to give detailed knowledge about single, binary and tertiary combinations of antimicrobial drugs, analytical methods, and patent search of these drugs.

Keywords: Antimicrobial resistance, Antimicrobial drugs, High-Performance Thin Layer Chromatography, High-Performance Liquid Chromatography, Stability Indicating Method, UV Visible Spectroscopy

INTRODUCTION: The primary cause of death and dysfunction is an infectious illness. Bacteria are becoming increasingly difficult to handle because of their resistance to the drugs (antibiotics) used to treat infections. Of the six main types of microorganisms, mainly bacteria, viruses, protozoa, fungi, algae and archaea have been associated with human disease ¹. Pathogens can be considered as all those microbes that have the potential to cause illness ². Less than 1% of bacteria are hazardous germs that can enter our bodies (the host) and cause illness.

Germs bring on infectious diseases like the flu and measles. Additionally, there is compelling evidence that bacteria may be the root of various chronic non-infectious disorders, including coronary heart disease and a few types of cancer. Microbes must enter our bodies in the proper chronological order to trigger an illness. They enter through a location called a portal of entry ³.

The four locations indicated below from which microbes can enter the body:

• The mouth and nose, e.g., the respiratory tract (where the influenza virus that causes the flu lives).
• Gastrointestinal tract, such as Vibrio cholera, which causes cholera, in the mouth or oral cavity.
• Infections of the urogenital tract, such as cystitis-causing Escherichia coli.
• Skin surface breaks that allow bacteria like Clostridium tetani, which causes tetanus, to enter.

Microbes need to do the following to infect us and cause illness ³:

• Reach their target site in the body.
• Connect with the target they are trying to infect to prevent them from being released.
• Multiply instantly
• Take nutrients from the host.
• Prevent and sustain the attack of the host immune system.

For some of the most common infectious diseases, there are vaccines and therapies available. Many are very cost-effective and reasonably priced, but due to prices and access issues brought on by underperforming healthcare systems, many are underutilized. The creation of new drugs and vaccines will continue to be vital tools for treating and preventing infections, but reducing the burden of infection will depend on how well these interventions are delivered ⁴.

Classification of Antimicrobial Drugs: Bacteria, viruses, fungi, and parasites are the four main microorganisms used in medicine.

FIG. 1: CLASSIFICATION OF ANTIMICROBIAL DRUGS ⁵

Antibacterial: An antibacterial agent prevents bacteria from proliferating and growing. Antibacterial agents are currently most frequently defined as substances that clean surfaces, eliminate potentially hazardous germs, and neutralize household cleansers. They should only be used if clinical or lab results indicate bacterial infection.

Based on their effectiveness and the amount of residue they leave behind, antibacterial agents can be categorized into two categories: Those in the first category function swiftly to eliminate bacteria, but they also vanish (via evaporation or disintegration) and leave no active residue behind (referred to as non-residue-producing). Aldehydes, alcohols, chlorine, and peroxides are a few examples of this category.

The second group is primarily made up of more recent substances that have a sustained action by leaving long-lasting residues on the surface to be cleaned (referred to as residue-producing). Benzalkonium chloride, triclosan and triclocarban are typical members of this group ⁵.

Antiviral agents: Medications in the antiviral medicine class are used to treat viral infections. Specific viruses enter our bodies and cause a variety of ailments. At the same time, the majority of antivirals focus on specific viruses, a broad-spectrum antiviral works against a range of viruses. Available antiviral drugs are primarily used to treat hepatitis b and c, influenza a and b, HIV and herpes viruses ⁶.

Antiparasitic agent: Antiparasitic drugs are treatments used to control and cure infections caused by parasites such as protozoa, helminths and ectoparasites. Various classes of antiparasitic medications treat a wide range of diseases brought on by parasites. This activity describes the uses, modes of action, side effects and contraindications of major antiparasitic drug classes as effective treatments for illnesses like malaria, pneumocystis, trypanosomiasis and scabies⁷.

Antifungal agent: Fungal infections are treated by antifungal drugs. Ringworm, yeast infections, and skin and nail infections are a few examples. Respiratory ailments can result from breathing in fungus spores. Immune deficiencies make people more vulnerable to fungal infections that call for antifungal medication. Antifungals are drugs that either eradicate or inhibit the development of the fungi that cause infections. They are also termed as antimycotic agents ⁸.

Different types of drugs and antifungal treatments come in many classes.

• Fluconazole and other azoles are fabricated, synthetic antifungals that stop the growth of fungi.
• Echinocandins, are more recent semi-synthetic antifungals that target and harm the fungus wall, including micafungin ⁸.

Pathophysiology of Antimicrobials: There are five basic ways that antimicrobials might alter the viability of microorganisms ⁹.

• Inhibition of cell wall synthesis
• Inhibition of microbial protein synthesis
• Interference with nucleic acid synthesis
• Inhibition of metabolic pathways
• Disruption and increased permeability of the cytoplasmic membrane

The following Table 1 represents the classification of antimicrobial agents and their mode of action.

TABLE 1: CLASSIFICATION OF SOME ANTIMICROBIAL AGENTS AND THEIR MODE OF ACTION ⁹

Antimicrobial agents have different sites and mechanisms of action. Fig. 2 represents the Mechanism and Site of Action of Antimicrobial Agents.

FIG. 2: MECHANISM AND SITE OF ACTION OF ANTIMICROBIAL AGENTS ⁹

Inhibition of Cell wall Synthesis ⁹: Interfere with peptidoglycan synthesis. Low toxicity causes cell lysis and includes penicillin and vancomycin as examples Ampicillin, methicillin and oxacillin are further antibiotics in the penicillin family (B- lactam). B-lactam antibiotics like penicillin and cephalosporins are the most frequently utilized antimicrobial medicines that prevent cell wall production. Direct inhibition of bacterial transpeptidases by B-lactam antibiotics is highly effective. B-lactam transpeptidase inhibitors prevent the maturation of peptidoglycan from its immature state; as a result, these enzymes are known as penicillin-binding proteins (PBPs). Glycopeptides are a different class of antibacterial drugs that prevent the production of cell walls. When compared to B-lactams, vancomycin's inhibition of peptidoglycan production results in a relatively slow inhibition. Vancomycin transfers the disaccharide of the peptidoglycan precursor to the developing glycan polymer of the cell wall by forming a stoichiometric 1:1 complex with the trans glycosylase enzyme and the peptidoglycan precursor. The glycopeptides prevent the transglucosylase and transpeptidase enzyme processes from completing the formation of the stiff cell wall peptidoglycan.

Microbial Protein Synthesis Inhibition ⁹: A variety of antimicrobial agents function by blocking the development of bacterial proteins (ribosome function). Some of these include aminoglycosides, macrolides and tetracyclines. In the initiation, elongation and termination phases, cytoplasmic components connect to particles with the help of ribosomes, to control the synthesis of proteins in microbes.

Interfere with mitochondrial prokaryotic (the 70s) ribosomes. While erythromycins, chloramphenicol, and clindamycin work at the level of 50S ribosomal subunits, tetracyclines, aminoglycosides and chloramphenicol act at 30S ribosomal subunits.Aminoglycosides kill bacteria by preventing protein synthesis. They achieve this by attaching to the 30S subunit ribosome, which prevents the initiation complex from functioning and prevents the creation of peptide bonds.

Most of the time, they target Gram-negative bacteria. Tetracyclines prevent aminoacyl t-RNA from attaching to the 30S ribosomal subunits, preventing bacteria from producing protein. They stop new amino acids from being added to the peptide chain. They are inconsistently effective against infections brought on by bacilli and cocci. By preventing the release of t-RNA after the transfer of its amino acids to the growing polypeptide, clindamycin prevents the creation of bacterial proteins.

Interference with Nucleic Acid Synthesis ⁹: Disrupt the transcription and replication of DNA. Some substances, such as rifamycin and quinolones, may be harmful to human cells. Synthetic nalidixic acids are quinolones. They belong to the same class of medications as levofloxacin, ofloxacin, and ciprofloxacin. They are antibacterial and work by preventing DNA gyrase from causing bacteria to synthesize DNA. It takes the enzyme DNA gyrase to unwind DNA strands so that they can be duplicated. Both Gram-positive and Gram-negative organisms are susceptible to quinolones antimicrobial effects. Rifampin inhibits the development of bacteria by tightly binding to their DNA-dependent RNA polymerase. This prevents the synthesis of RNA in bacteria. Rifampin works against viruses using a different way. It prevents a crucial step in the formation of polioviruses.

Inhibition of Metabolic Pathways ⁹: Sulphonamides and trimethoprim prevent the synthesis of nucleotides, which prevents the production of nucleic acids. Sulphonamides compete for the enzyme's active center and replace PABA. Overuse of PABA can negate the sulphonamides inhibitory effects on bacterial growth. Sulphonamides are bacteriostatic medications that work well against both Gram-positive and Gram-negative bacteria.

Both Gram-positive and Gram-negative organisms are susceptible to the drug trimethoprim. The substance prevents dihydro folic acid reductase from functioning. This enzyme reduces tetrahydro folic acid from dihydro folic acid, inhibiting DNA and purine synthesis.

Disruption and Increased Permeability of Cytoplasmic Membrane ⁹: Influence modifications in membrane permeability.

1. Cause cell lysis and/or metabolite loss.
2. Several antibiotics are found in polypeptides.
3. Polymyxin, for instance (antibacterial)

By attaching to the cell membrane, polymyxin increases its permeability. Cell death results from water uptake. They act as detergents because they are cationic, basic proteins (surfactants). Acute renal tubular necrosis and neurotoxicity are two possible side effects. It is commonly used in topical first-aid preparation.

Management of Antimicrobial Therapy:

Introduction of Antimicrobial Therapy: The urgency of the condition should determine when to begin initial therapy. In severely ill patients, such as those in septic shock, febrile neutropenic patients and patients with bacterial meningitis, empiric therapy should be initiated right after or concurrently with the collection of diagnostic specimens. Two important examples of this idea are subacute bacterial endocarditis and vertebral osteomyelitis/diskitis.

Antibiotic therapy should be delayed until numerous blood cultures, disc space aspirate specimens and/or bone biopsy specimens have been collected (in the case of endocarditis). Antibiotic medication should be delayed until the patient has symptoms, which frequently take days to weeks to manifest in patients with these illnesses. In these circumstances, if antimicrobial medication is initiated too soon, it may inhibit bacterial growth and render a microbiological diagnosis which is crucial for monitoring these patients care impossible. To recover, these individuals must receive directed antimicrobial therapy for several weeks to months ¹⁰.

Antimicrobial agents:

Combination Therapy ^10-11:  A combination of two or more antimicrobial medicines is advised in a few circumstances, even though single-agent antimicrobial therapy is normally favoured.

Treatment of Microbial disease using More than one Antimicrobial agent: Certain lactams and aminoglycosides work in synergy to combat a wide range of gram-positive and gram-negative bacteria. They are used to treat serious infections where quick killing is crucial (e.g., treatment of endocarditis caused by Enterococcus species with a combination of penicillin and gentamicin). Gentamicin is bactericidal when combined with penicillin; penicillin alone is simply bacteriostatic, while gentamicin alone has no discernible effect. A comparable synergistic combination of penicillin or ceftriaxone with gentamicin for two weeks can be beneficial as penicillin or ceftriaxone alone in treating endocarditis brought on by some streptococci. Similar synergistic combinations can also be used to shorten the period of antimicrobial therapy.

To Treat Polymicrobial Diseases by Broadening the Antimicrobial Spectrum Beyond what can be achieved with a Single Agent: A combined regimen may be chosen when illnesses are suspected to be brought on by multiple organisms since it would broaden the antimicrobial range beyond what can be attained by a single drug. For instance, most intra-abdominal infections are frequently caused by multiple organisms with gram-positive cocci, gram-negative bacilli, and anaerobes. These situations may benefit from using antimicrobial combinations such as fluoroquinolone plus metronidazole or a third-generation cephalosporin which are sometimes more inexpensive than an equivalent single agent (e.g., a carbapenem).

To Inhibit Resistance from Developing: Antimicrobial medication typically exerts selective pressure on bacteria, leading to resistant variants. Suppose the mechanisms of resistance to the two antimicrobial agents are dissimilar. In that case, a mutant strain's likelihood of being resistant to both antimicrobial agents is significantly lower than its likelihood.

Combining therapy would improve the possibility that at least one drug will be effective, preventing the resistant mutant population from becoming the dominant strain and resulting in therapeutic failure. Because of this, combination drug therapy is accepted as the gold standard for treating disorders, including tuberculosis and the human immunodeficiency virus (HIV) when treatment duration is likely to be protracted.

Prophylactic use of Antimicrobial Drugs ¹¹: This refers to using antimicrobial drugs for prevention rather than the treatment of infections.

To preserve against certain microorganisms:

1. Long-acting penicillin G is used to prevent group A streptococci infections in patients with a history of rheumatic heart disease.
2. Procaine penicillin is advised for the prevention of gonorrhoea or syphilis after contact with an infected person.
3. Prevention of recurrent urinary tract infections caused by coli, trimethoprim-sulphamethoxazole is used.

Prevention of Infections among Patients at High Risk:

1. Preventing endocarditis by pre-treating individuals with valvular abnormalities who are getting dental work done, having tonsils removed, or having endoscopies with a high risk of bacteremia.
2. Patients enduring cancer chemotherapy or organ transplant.
3. To prevent wound infections following a variety of surgical procedures.
4. Dirty, filthy surgical procedures (e.g., resection of the colon). In clean surgical procedures, chemotherapy should not be performed consistently.

The use of antimicrobials in this way is the most widespread and prolonged. A wound infection occurs when several germs are present in the wound at the time of closure. Antibiotics must be used wisely and effectively in this case. They should be given immediately before and shortly after the procedure.

Antimicrobial therapy should not be continued for longer than 24 hours to prevent the development of resistant strains. The effectiveness of the antibacterial medication should successfully reduce the risk of surgical site infection. First-generation cephalosporins are now being used for chemoprophylaxis.

Patent Search for Antimicrobial Drugs: Over the past couple of years, much research has been done on antimicrobial drugs and many patents that can be beneficial for research purposes. Table 2 Represents a list of the patent search for antimicrobial drugs.

TABLE 2: PATENTS OF ANTIMICROBIAL DRUGS

List of Validated Analytical Methods of Antimicrobial Drugs: Analytical methods need to be validated or revalidated before their introduction into routine analyses ³³. This review article's primary goal was to examine how the drug was developed and validated from the beginning of the formulation process to the final commercial batch of the product.

Validation is crucial to the efficient operation of pharmaceutical companies. Validation was done at every level, from the raw materials to the finished product. The technique was appropriately established, and validation parameters are described in terms of precision, accuracy, the limit of detection (LOD), the limit of quantitation (LOQ), ruggedness and system suitability testing with the use of specific drugs as examples ³⁴.

ICH Q2(R1) guidelines also mention that analyses must adhere to GMP and GLP practices; protocols and acceptance criteria must be followed when developing analytical methods in the routine and stability analysis, and all validation parameters are utilized.

However, UV spectrophotometry, RP-HPLC, and HPTLC stability indicate the RP-HPLC method. Table 3 represents reported methods for assessment of combinations of antibacterial drugs. Table 4 shows reported methods for assessment of a combination of antifungal drugs. Table 5 depicts reported methods for assessment of combinations of anti-viral drugs. Table 6 illustrates reported methods for assessing combinations of anti-parasitic drugs are shown below.

TABLE 3: REPORTED METHOD FOR ASSESSMENT OF COMBINATIONS OF ANTIBACTERIAL DRUGS

TABLE 4: REPORTED METHOD FOR ASSESSMENT OF COMBINATION OF ANTIFUNGAL DRUGS

TABLE 5: REPORTED METHOD FOR ASSESSMENT OF COMBINATIONS OF ANTI-VIRAL DRUGS

TABLE 6: REPORTED METHOD FOR ASSESSMENT OF COMBINATIONS OF ANTI-PARASITIC DRUGS

CONCLUSION: The present review depicts how antimicrobial drugs affect the viability of microorganisms and their management and initiation therapy antimicrobials. This review work also sheds light on the prophylactic use of antimicrobial drugs. The present review gives information about the various analytical methods reported for determining all combinations of antimicrobial drugs along with the patents and therapeutic effects. The current review will be a reference for further development and validation of the analytical methods of antimicrobial combinations and provides detailed knowledge about the characteristics of all antimicrobial drugs.

ACKNOWLEDGEMENT: The authors are thankful to the Parul Institute of Pharmacy, Parul University, for providing a necessary source for the design of the current review article.

CONFLICTS OF INTEREST: No conflicts of interest are listed by the author for the current review article.

REFERENCE:

1. Wilson, Michael and Wilson, Philippa J. Nonadherence to antimicrobial drugs a systematic review and meta-analysis. Microbes and Infectious Diseases" Close Encounters of the Microbial 2021; 48: 234-678.
2. Dedania ZR, Dedania RR and Patel U: Tiffany Essentials of medical pharmacology Seventh Edition Jaydeep Brothers Medical Publishers Pvt Ltdan Introduction to Infectious Disease November 2018; 25: 78-90.
3. Chakrabarty J, Rao S and Modi BP: Microbiology SocietyMicrobes and DiseaseDrugs 2022; 51: 99–136.
4. Holmes KK, Bertozzi S and Bloom BR: Major Infectious Diseases: Key Messages from Disease Control Priorities, Third Edition Washington the International Bank for Reconstruction and Development 2021; 23: 345-678.
5. Aziz MA, Fritsche TR, Howard DH, Ibrahim KH, Koeth LM, Low DE, Oliar P, Palmisano L, Rennie RP and Sader HS: Scott II RD. Alliance for the Prudent Use of Antibiotics 2019; (41): 28-98.
6. Wikipedia contributors’ Antiviral drug. Retrieved 2022; 16: 58-456.
7. Campbell S and Soman Faulkner K: Antiparasitic Drugs Stat Pearls Treasure Island Stat Pearls Publishing 2022; 12: 23-56.
8. Veterinary and Oltean MEG:  Nica Antifungals What They Treat, How They Work & Side Effects 2021; 26: 156–167.
9. Jaka, Hm and Liwa: Anthony, title antimicrobial resistance: Mechanisms of Action of Antimicrobial Agents 2018; 5: 877-879.
10. Leekha S, Terrell CL and Edson RS: General principles of antimicrobial therapy. Mayo Clinic Proceedings 2020; 86: 156–167.
11. Wikipedia contributors and Gilman's The Pharmacological Basis of Therapeutics. In Wikipedia, the Free Encyclopaedia 2022; 16: 737-738.
12. Debashish Datta Murali Krishna Danto Pollepeddi Lakshmi Narayana Sharma and Brij Kishore Mishra: Method for manufacture of ceftriaxone sodium US7470786B2 2020.
13. Clindamycin hydrochloride injection and preparation method thereof CN101756897B 2019
14. Edward M. Rudnick James D. IsbisterDonald J. Treacy J and Sandra E: Wassink US6663890B2 2001.
15. William W: Armstrong Doxycycline compositions US4086332A 2017.
16. Kae-Shyang ShihLie-Rong ChenChing-Wei and LiuChia-Lin J: Wang US5710280A 1996.
17. Glen S: KwonBong K. Yoo US6413537B1 2017.
18. Zorn Ralph Allan Ronald C. Malzahn Austin M. Hanson: Bacitracin product and processes US2985534A 2010.
19. Production process of compound preparation of ceftriaxone sodium and tazobactam sodium for injection CN101537009A 2009.
20. Mahmut BelgicFilm tablet formulations comprising cefuroxime acetyl and clavulanic acid WO2013151516A1 2017.
21. Preparation method of clindamycin phosphate solution formulation and its applying sheet CN1839872A 2019.
22. Dan-Gabriel Vulpescu Pharmaceutical composition containing clindamycin and clotrimazole DE19737348C2 2019.
23. Neeta Gupta Simrata Bedi Jyoti Srivastava and Vinod Kumar Arora: Topical pharmaceutical composition comprising nanosized silver sulfadiazine and chlorhexidine gluconate WO2012017349A3 2020.
24. Kevin H: Storm Creighton P. Conley and John A. Roush: Compositions and methods of treatment comprising amoxicillin and potassium clavulanate with xanthan US7217430B2 2020.
25. Rajan Singh Compositions and methods for treating or preventing metabolic syndrome disorders US9682093B2 2017.
26. Imipenem and cilastatin sodium pharmaceutical composition liposome injection CN102266326B 2017.
27. Selman A Waksman Hubert A Leche Valier  Neomycin and process of preparation US2799620A 2013.
28. Medicine composition and preparation method and purpose CN103127509A 2016.
29. Shirish Bhagwanlal Modi Madhu Kant Man Sukh Lal Doshi Milind and Dattatraya Joshi: Novel topical microbicidal compositions WO2002094179A2 2022.
30. Mendoza Ivonne Arellano Method of maintenance therapy of melasma and use of a mixture of fluocinolone acetonide, tretinoin hydroquinone BRPI0719454A2 2017.
31. Shiladitya Sengupta Suresh Ramesh Lal ChawraiShamika Ghosh Sumana Ghosh Nilu Jain and Suresh Sadhasivam: Besifloxacin for the treatment of resistant acne ES2784307T3 2015.
32. Zengxia Wang Xiao Bing LiFen Luo Changlong Li Yanwei Xu Long Chen Polymyxin b sulfate crystal and preparationUS20190256557A1 2016.
33. García, Pedro, Buffoni, Ernesto Gomes, Fabio and Vílchez: Analytical Method Validation 2018; 11-89.
34. Sharma, Shivani and Goyal, Swapnil and Chauhan, Kalindatitle: A review on analytical method development and validation, volume 10, journal International Journal of Applied Pharmaceutics 2019; (11): 8-12
35. Ceftriaxone: Therapeutic uses, Dosage & Side Effects by Doctor Alert 2017;(10): 124-235
36. Business Bliss Consultants FZE. RP-HPLC-UV Method for Simultaneous Estimation of Ceftriaxone 2018; (16): 234-456.
37. Patel KY, Dedania ZR, Dedania RR and Patel U: QbD approach to HPLC method development and validation of ceftriaxone sodium. Future Journal of Pharmaceutical Sciences 2021; 71: 1-56.
38. Murphy PB and Bistas KG: RPHPLC method development for determination of Clindamycin in Stat Pearls 2022; 14: 2-34.
39. Gupta A, Khan MA and Faustino PJ: Development and application of a validated HPLC method for the determination of clindamycin palmitate hydrochloride in marketed drug products and optimization of the current USP methodology for assay. JAS 2018; 9: 24-66.
40. Nataraja KS, Raju G and Narasimha Surya AB: UV spectrophotometric method development for estimation of clindamycin phosphate in bulk and dosage form 2022; 4: 164-167.
41. Butu M, Negoescu C and Caunii A: Cristina HPLC method development for determination of doxycycline in human seminal fluid. J of Chromato 2021; 20: 23-98.
42. Shahin, Vemavarapu and Satish Kumar: Shadan Simultaneous Determination of Clarithromycin and Esomeprazole Plasma after Oral Administration by Reverse Phase HPLC Method Khairtabad, Hyderabad 2017; 7: 345-678.
43. Oltean and Nica Development and validation of A RP-HPLC method for the quantization studies of metronidazole in tablets and powders dosage forms 2019; 23: 23-45.
44. Shivani Goyal, Swapnil and Chauhan: Development and Validation of UV Spectroscopic Method for Estimation of Doxycycline 2021; 17: 2-45.
45. Mohammad Younus, T. Karmarkar Reddy and Y. Ravindra Reddy: ArifHPLC method development for determination of doxycycline in human seminal fluid. Journal of Chromatography 2020; 41: 287-578.
46. Kagawa and Salgado: Harim Quantification of doxycycline Hyclate in tablets by HPLC–UV method. Journal of Chromatographic Science 2019; 51: 919-925.
47. Wald DS, Law M, Morris JK, Best wick JP and Wald NJ: the Prevention Randomized Clinical Trial. J Am Heart Assocby Bacitracin 2022; 6: 287-834.
48. Pavli V: Kmetec Optimization of HPLC method for stability testing of bacitracin. JPBA 2021; 24: 921-85.
49. Gandhi, Santosh and Kapoor and Barka: Development and Validation of UV Spectroscopic Method for Estimation of Baricitinib. J of Drug Delivery and Thera 2016; 31: 25-98.
50. Murali Krishna DantoPollepeddi Lakshmi Narayana Sharma Cefoperazone and Tazobactam for injection therapeutic use 2019; 24: 452-82.
51. Vipul J. Panchal, Hemant T. Desai and Ashwin G: Dave development and validation of stability indicating method for simultaneous estimation of ceftriaxone and tazobactam injection using RP-UPLC method 2016; 14: 238-2405
52. Shrestha B, Bhuiyan NR and Sinha BNS: imultaneous determination of Ceftriaxone and Tazobactam in injectables by UHPLC method. Pharmaceutical Methods 2019; 14: 46-51.
53. Modi, Vairale and Brogdon: Application of an LC–MS/MS method for the analysis of Cefuroxime Acetyl and Potassium Clavulanate therapeutic use 2021; 17: 345-678.
54. Dalvi SD, Jadav DD, Gedi SV, Patil LD and Kadam: Simultaneous determination of Cefuroxime acetyl and Potassium Clavulanate in pharmaceutical dosage form by RP-HPLC. Inter J Pharm and Pharm Sci 2018; 5: 179-81.
55. Mary K, Kumar and Chandana P: Saar biotech Clindamycin Phosphate and Adapalene Gel Therapeutic use 2017; 4: 46-51.
56. Samir Chaudhary and Modi JI: Shaikh RP-HPLC method development and validation for simultaneous estimation of clindamycin phosphate and Adapalene in the Pharmaceutical dosage form 2014; 4: 160-742.
57. Mauley Patel, Komal Patel and Dhaval Patel: Development and validation of analytical method for simultaneous estimation of Amoxicillin Trihydrate and Potassium Clavulanate 2022; 27: 345-354.
58. Gujral RS and Haque SM: Simultaneous determination of potassium clavulanate and amoxicillin trihydrate in bulk, pharmaceutical formulations and human urine samples by UV spectrophotometry 2016; 6: 335-675.
59. Bari S, Sathe S, Jain P and Zouboulis Clindamycin: phosphate/tretinoin gel formulation in the treatment of Acnevulgaris 2018; 9: 2931–2937.
60. Roy C, Chakrabarty J, Rao S, Modi BP and Vairale A: Residue determination of clindamycin phosphate and tretinoin on the surface of manufacturing equipment by RP-HPLC. J Pharm 2021; 12: 35-98.
61. Balfour and Bryson: Brogdon Imipenem/cilastatin: an update of its antibacterial activity. Pharmacokinetics and Therapeutic Efficacy in the Treatment of Serious Infections 2022; 11: 99-136.
62. Murali D, Rao Stability Indicating RP-HPLC Method for the Simultaneous Estimation of Imipenem and Cilastatin in Injection Formulations 2016; 16: 234-678.
63. Karunanidhi Santana Lakshmi and Sivasubramanian Lakshmi: First-order derivative ultraviolet spectrophotometry of imipenem–cilastatin formulations. J of Taibah University Medical Sciences 2017; 13: 178-8.
64. Srinivasan R, Mary KL, Kumar DR and Chandana A: new RP-HPLC method for the simultaneous estimation of imipenem and cilastatin in the pharmaceutical dosage form. Int J Adv Pharmaceutical Sci 2021; 52: 240-478.
65. Balfour, Bryson and Brogdon Imipenem/cilastatin: an update of its antibacterial activity. Pharmacokinetics and Therapeutic Efficacy in the Treatment of Serious Infections 2019; 23: 99-136.
66. Mustafa A, Ali H, Bibi R, Hassan A and Khan S:  Simultaneous Determination of Amoxicillin, Clarithromycin and Esomeprazole in Mice Plasma after Oral Administration by Reverse Phase HPLC Method 2021; 12: 114-456.
67. Andersson T, Ross K and Hassan-Alin M: Drug interaction studies of esomeprazole with amoxicillin and clarithromycin gastroenterology 2018; 12: 234-345.
68. Harmita H, Suryadi H, Jadav DD, Gedi SV and Patil LD: Povidone Iodine, Tinidazole, Sucralfate. JETIR 2020; 21: 129-34.
69. Ahmed S, Rizwan I and Vani MA: Basha Stability indicating method development and validation of sucralfate and oxetacaine in bulk and marketed formulation by RP-HPLC 2022; 6: 21-33.
70. Govindarajan A and Bistars KG: Fluconazole. In: Stat Pearls. Treasur Island Stat Pearls Publishing 2022; 12: 1-5.
71. Rajesh Sharma, Sunil Khanna and Ganesh Prasad Mishra: Bacitracin (Topical) Bacitracin Monograph for Professionals 2021; 5: 1269-04.
72. Mohammad Younus, T. Karunakar Reddy, Y. Ravindra Reddy MD and Nasiruddin Arif: HPLC Analysis of Drug Fluconazole and Related Impurities on Coresep 100 Mixed-Mode Column Chromatography 2019; 12: 234-398.
73. Hemant T. Desai and Ashwin G: Cerner Multum by Drugs and Content Service Article on 2022; 24: 23-89.
74. Llabot, Allemande DA, Manzo RH and Langhi MR: HPLC method for the determination of nystatin in saliva for application in clinical studies. Journal of Pharmaceutical and Biomedical Analysis 2020; 3:526-30.
75. Rodino S, Butu M, Negoescu C, Caunii A, Cristina RT and Butnariu M: Spectrophotometric method for the quantitative determination of nystatin antifungal agent in Pharmaceutical Formulations 2019; 9:1215-22.
76. Swapnil and Chauhan: Cerner Multum ASHP Vaginal anti-infectives 2017; 6: 335-457.
77. Raja Meena, Rama and Muthu Lakshmi: RP-HPLC method development and validation for estimation of Clindamycin phosphate and Clotrimazole in pharmaceutical dosage forms 2021; 4: 141-6.
78. Nataraja KS, Raju G and Narasimha Surya: UV spectrophotometric method development for estimation of clindamycin phosphate in bulk and dosage form 2022; 16: 87-678.
79. Sohail M: Patel Development and Validation of UV Spectrophotometric Method for Simultaneous estimation of Terbinafine hydrochloride and Mometasone furoate in Combined Dosage for 2019; 6: 251-259.
80. Mehul M. Patel and Heta D. Patel: Journal of the Chilean Chemical Society 2015; 234-897.
81. Treatment of systemic fungal infections: recent progress and current problems T J Walsh 2020; 45: 34-56.
82. Patel AJ: Development and validation of stability indicating HPTLC method for simultaneous estimation of fluocinolone acetonide and miconazole nitrate in the ointment. Austin Chromatographer 2017; 1(5): 1023-32.
83. Brent Jens, M. H Yeung-Yue, K. A Lee, P. C and Tyring: Recurrent genital herpes treatments and their impact on quality of life. Pharmacoeconomics 2021; 21: 853–863.
84. Vishnu Melaka, Medi cherla, Rao Sharna and Srinu Babu: Development and validation of LC method for the determination of famciclovir in Pharmaceutical Formulation using an Exper Design 2018; 15: 58-67.
85. Mayas VI, Pati NI, Yadav GO and Gupta VR: Method development and validation of RP-HPLC Method for famciclovir 2016; 14: 1415-24.
86. Poulter NR, Wedel H, Dalhoff B, Sever PS, Beeves and Caulfield M: Treatment of patients with genotype 3 chronic hepatitis current and future therapies. Liver International Official J of the International Association for the Study of the Liver 2022; 78: 1478-3231.
87. Zaid, Giza and Attia: Efficient HPTLC-dual wavelength Spectro densitometric method for simultaneous determination of sofosbuvir and daclatasvir: Biological and pharmaceutical analysis. Journal of Pharmaceutical and Biomedical Analysis 2018; 15: 358-65.
88. Tannak, Hamdan and Elissa: Development of a robust UPLC method for simultaneous determination of a novel combination of sofosbuvir and daclatasvir in human plasma: Clinical Application to Therapeutic drug Monitoring 2018; 21: 67-89.
89. Eberle Solei Treatment for human immunodeficiency virus (HIV) infection. The Western J of Med 2017; 8: 175–176.
90. Mishra T and Shrivastava PS: Validation of simultaneous quantitative method of HIV protease inhibitors atazanavir, darunavir and ritonavir in human plasma by UPLC-MS/MS. The Scientific World Journal 2018; 64: 23-78.
91. Raju P, Thejomoorthy K and Prasanna PS: Development and Validation of New Analytical Method for the Simultaneous Estimation of Darunavir and Ritonavir in Pharmaceutical Dosage Form. International Journal of Indigenous Herbs and Drugs 2021; 5: 49-57.
92. Chandler, Salkowski, M. S Jenckes, M. W Torben son, M. S. Her long HF Bass EB and Gabo KA: Treatment of chronic hepatitis C: a systematic review 2020; 36: 135-144.
93. Mohammed BS, Derayea SM and Hamad AE: Feasible TLC-Spectro-Densitometry Technique for Simultaneous Determination of Two Hepatitis C Antiviral Drugs, Sofosbuvir and Simeprevir: Application to Combined Pharmaceutical Dosage Forms and Human Plasma. Journal of Chromatographic Science 2021; 59: 576-83.
94. Application of different spectrophotometric methods for quantitative analysis of direct-acting antiviral drugs Simeprevir and sofosbuvir. Spectrochemical Acta Part A: Mol and Biomolecular Spectroscopy 2022: 272-1210.
95. Crosby, Kipke MD and Kubica: The use of pre-exposure prophylaxis increases the odds of condomless anal sex among young men who have sex with men of colour. 2020; 17: 100-101.
96. Sharma R and Gupta: a Validated RP-HPLC method for simultaneous estimation of emtricitabine and tenofovir disoproxil fumarate in a tablet dosage Form. Eurasian Journal of Analytical Chemistry 2019; 1(4): 276-84.
97. Purnima BV, Reddy TV, Rao YS, Ram G and Ramachandran D: Stability indicating RP-UPLC method for assay of emtricitabine and tenofovir disoproxil fumarate in bulk and dosage forms. American Journal of Analytical Chemistry 2015; 6: 807-8790.
98. Kempe Medical Management of Human Immunodeficiency Virus Infection. Indian Journal of Ophthalmology 2019; 22: 193–278.
99. Patel Hemant, Shah Suman, Gajera and Patel HD: Development and validation of rp-hplc method for simultaneous determination of related substances present in the pharmaceutical dosage form of emtricitabine, tenofovir alafenamide and dolutegravir. Journal towards Excellence 2020; 627-644.
100. Forde and Bhattacharya: Treatment of Hepatitis C Virus (HCV) Genotype 1 Disease. Current treatment options in infectious diseases 2017; 9: 262–276.
101. Attia KA, El-Oley A, Ramzi S, Abdelazim AH, Hasan MA and Abdel-Kareem RF: Simultaneous determination of elbasvir and grazoprevir in their pharmaceutical formulation by synchronous fluorescence spectroscopy coupled to dual wavelength method. Spectrochemical Acta Part A: Molecular and Biomol Spectr 2021; 5: 248-1191.
102. Bharti, Bharti and Khurana S: Worm Infestation: Diagnosis, Treatment and Prevention 2018; 85: 1017–1024.
103. Bonito PS, Anclote VL and Takenaga OM: Simultaneous liquid chromatography-tandem mass spectrometric determination of albendazole sulfoxide and albendazole Sulfone in Plasma 2022; 57: 237-45.
104. Martin and Robert: Control of nematode parasites with agents acting on neuro-musculature systems. Lessons for Neuropeptide Ligand Discovery 2017; 69: 138–154.
105. Devaki NV, Rao VM. Chromatographic quantification of ivermectin and praziquantel in the tablets using stability indicating RP-HPLC Method 2019; 25: 254-61.
106. Campbell S and Soman-Faulkner K: Novel RP-HPLC method for simultaneous determination of Clindamycin and Dapsone in tablet dosage form. Int J of Biological & Pharmaceutical Research Antiparasitic Drugs Stat Pearls 2022; 345-678.
107. Padivitage N, Adhikari S and Rustom AM: Simultaneous determination of ivermectin, Clorsulon and their related substances in an injectable finished product by a stability-indicating RP-HPLC method. Journal of Pharmaceutical and Biomedical Analysis 2022; 20: 114-580.
     

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     How to cite this article:

     Tyagi A and Dave H: Analytical method development and validation of anti-microbial formulations - a review. Int J Pharm Sci & Res 2023; 14(9): 4344-57. doi: 10.13040/IJPSR.0975-8232.14(9).4344-57.

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