Formulation And Evaluation of an Anti-Nerve Impulse Cream Containing Benzocaine and Aceclofenac

Mohammed Sufiyan Raees Ahmed, Shaikh Faizan, Rohan Chavan, Ashish Kulkarni, Piyush Raut, Nikhil Petkar,

doi:10.5281/zenodo.17680351

Review Paper | Open Access
Volume 03 | Issue 11 | Article Id IJPS/250311441

Formulation And Evaluation of an Anti-Nerve Impulse Cream Containing Benzocaine and Aceclofenac
Mohammed Sufiyan Raees Ahmed* Shaikh Faizan Rohan Chavan Ashish Kulkarni Piyush Raut Nikhil Petkar
Valmik Naik College of Pharmacy.

Abstract

A. A Complex Series Of Events That Trigger Peripheral Pain Receptors And Send Messages Via The Central Nervous System Result In Pain And Inflammation. With The Benefit Of Localised Site-Specific Targeting Of The Intended Location, Topical Medication Administration Provides An Alternative To Oral And Injectable Dose Forms By Avoiding First-Pass Metabolism In The Liver And Sparing The Gastrointestinal System From Discomfort. The Goal Of This Review Is To Develop And Assess An Antinerve Impulse Cream That Combines The Effects Of Aceclofenac, A Nonsteroidal Anti-Inflammatory Drug (Nsaid), And Benzocaine, A Local Anaesthetic, Using A Dual-Action Drug Approach To Produce An Effective, Synergistic Anti-Inflammatory And Analgesic Impact With Less Adverse Effects On Other Body Areas. Benzocaine Is A Well-Known Anaesthetic That Is Frequently Used To Treat Dental Issues, Ear Pain, And Mouth Ulcers. Benzocaine Has Been Identified As A Na+ Channel Blocker And An Anaesthetic Agent In Surgical Procedures, Along With Lidocaine And Other Local Anaesthetics. In Addition To The Requirements For Formulation Development And The Essential Quality Control Tests (Viscosity, Spreadability, Invitro Diffusion, Etc.), Profiles Of The Drugs To Be Included Are Described, Along With An Outlook On The Potential For Next- Generation Topical Systems Like Nanoemulsions And Liposomal Carriers.

Keywords

Benzocaine, Aceclofenac, Topical Formulation, Analgesic Cream, Antiinflammatory, Nerve Impulse Blockade, Evaluation Parameters

Introduction

The Most Common Reason People Seek Medical Attention Is Pain. Effective Control Is Essential For Enhancing Quality Of Life And Accelerating Healing. When Used Over An Extended Period Of Time, Traditional Oral Painkillers Frequently Result In Serious Adverse Effects, Such As Stomach Irritation, Liver Damage, Or Systemic Issues. As A Result, Using Medications For Pain And Inflammation Topically Has Become A Crucial Tactic. Topical Creams Are Semisolid Emulsions That Are Intended To Penetrate The Skin And Deliver Active Ingredients Directly To The Site Of Action. Better Patient Compliance, A Quick Start Time, And Localized Effects Are All Made Possible By This. We Selected Two Medications: Aceclofenac, A Strong Cox2 Inhibitor That Lowers Edema And Inflammation, And Benzocaine, Which Blocks Peripheral Nerve Impulses. The Purpose Of This Review Is To Outline The Procedures For Creating

Pain Transmission and Nerve Impulse Mechanism:

When Heat, Mechanical Force, Or Chemicals Trigger Nociceptors, Pain Begins. By Activating Voltage-Regulated Sodium Channels, These Stimuli Cause The Neuronal Membrane To Depolarize. Action Potentials, The Electrical Signals That Occur, Travel Up The Nerve Fibers To The Spinal Cord And Ultimately To The Brain, Which Is Where We Experience Pain. By Completely Stopping This Depolarization, Blocking Sodium Channel Activity Effectively Stops The Pain Signal From Spreading. This Is Exactly How Local Anesthetics, Such As Benzocaine, Function. Combining An Nsaid (Such As Aceclofenac) With A Local Anesthetic Significantly Increases The Overall Analgesic Power Since Inflammatory Substances Like Prostaglandins And Bradykinin Also Make Nociceptors More Sensitive.

Overview Of Topical Drug Delivery:

Topical Delivery Aims To Place The Drug Exactly Where It's Needed In The Skin's Various Layers. The

Benefits Are Clear:Bypassing Firstpass Metabolism In The Liver.

Layers Of Skin. The Advantages Are Evident: Avoiding The Liver's First-Pass Metabolism. Decreased Chances Of Toxicity And Systemic Exposure. High Patient Convenience And Simple

Application. The Stratum Corneum, The Skin's Thick Outer Layer, Medication Solubility, And Stability Are The Key Challenges Formulation Scientists Still Confront. Creams, Which Are Emulsions Of Oil And Water, Provide The Perfect Hydration And Consistency For Administering Both Fat-Loving (Lipophilic) And Water-Loving (Hydrophilic) Medications.

Benzocaine:

The Source Of Benzocaine, An Estertype Local Anesthetic. It Functions By Preventing The Ion Flow Required To Initiate And Conduct A Nerve Impulse And Stabilizing The Neuron Membrane. Ethyl 4-Aminobenzoate Is The Chemical Name. C9h11no2 Is The Molecular Formula. 165.19g/Mol Is The Molecular Weight.

1. Action Mechanism:

Voltagegated Sodium Channels In The Neuronal Membrane Are Reversibly Blocked By Benzocaine. This Blocks The Nerve Impulse From Spreading And Prevents Depolarization. Because Benzocaine Is Less Soluble In Water Than Lidocaine, It Is Ideal For Topical Use Where Little Absorption Into The Bloodstream Is Required.Acology Of Benzocaine:

1. Pharmacokinetics :

Absorption: Minimal Into The Systemic Circulation Through Intact

Skin.Well Absorbed Through Mucaous Membranes And Damaged Skin .Depend On Site Of Application Concentration And Duration Of Contact Metabolism: Broken Down By Plasma Esterases Into Paba And Ethanol.Paba Is The Major Metabolite And Can Cause Allergic Reaction In Some Individuals Elimination: Excreted Mostly In The Urine.Mainly As Paba Conjugate ,Very Short Due To Rapid Metabolism.

1. Therapeutic Uses :

Topical Medicines For Minor Burns, Bug Bites, Sore Throats, Dental Pain Alleviation, And General Local Pain Frequently Contain It. Discovered In Topical Pain Management: Used To Treat Sunburns, Mild Burns, Wounds, Scratches, And Insect Bites. Found In Gels, Lozenges, And Sprays To Treat Denture Discomfort, Mouth Ulcers, Sore Throats, And Toothaches. Used In Ear Drops To Treat Ear Pain Or Discomfort Brought On By Ear Infections Or Earwax Removal; Used In Ointments Or Suppositories To Treat Hemorrhoids Or Anal Fissures. Used To Numb Mucosal Membranes Before To Small Surgical Or Diagnostic Procedures (Such As Endoscopy, Catheter Insertion, Or Throat Swabs).

Pharmacology Of Aceclofenac :

Aceclofenac Is A Phenylacetic Acid Derivative And A Powerful Nsaid That Provides Both Pain Relief And Fever Reduction.

Chemical Name: 2[2[2(2,6dichlorophenyl)Amino]Phenyl]Acetoxyacetic

Acid Molecular Formula: C16h13cl2no4

Molecular Weight: 354.18g/Mol

1. Mechanism Of Action :

Ithe Cyclooxygenase Cox 1 And Cox 2 Enzymes Are Inhibited By Aceclofenac. The Generation Of Prostaglandins, The Primary Molecules Responsible For Inflammation And Discomfort, Is Significantly Reduced By This Action. Additionally, It Aids In Lowering Levels Of Inflammatory Cytokines Such As Tumor Necrosis Factors And Interleukin. The Primary Mechanism Of Action Of Ace Is The Suppression Of Prostaglandin (Pg) Production. The Cyclooxygenase (Cox) Enzyme, Which Is Involved In The Manufacture Of Pg,

Is Inhibited By Ace. Unstimulated Bovine Aorta Coronary Endothelial Cells In Vitro Showed That Ace Was More Selective For Cox-2 Than Cox-1. Additionally, Ace Prevents The Production Of Interleukins, Tumor Necrosis Factors, And Inflammatory Cytokines. Additionally, It Has Been Suggested That Ace Affects Neutrophil Cell Adhesion Molecules [

1. Pharmacokinetics :

Absorption: Effectively Passes Through The Skin's Barrier. Bioavailability Of Roughly 100%. Peak Plasma Concentration (Tmax) Was Attained 1.25–3 Hours Following Oral Administration. Metabolism: Diclofenac And Other Hydroxymetabolites Are Mostly Produced In The Liver. Metabolites Undergo Further Transformation Into Conjugated And Hydroxylated Forms. Elimination: Removed By Bile And Urine. 70–80% Of These Are Hydroxylated Metabolites.

1. Therapeutic Uses :

It Treats Conditions Like Osteoarthritis, Rheumatoid Arthritis, And Ankylosing Spondylitis. Applying It Topically Is A Crucial Way To Avoid The Major Gastrointestinal Side Effects Associated With Taking The Drug Orally.

Parameter	Benzocaine	Aceclofenac
Chemical Formula	C9h11no2	C16h13cl2no4
Molecular Weight	165.19 G/Mol	354.19–354.2 G/Mol
Drug Class	Ester Local Anesthetic (Amino Ester)	Nsaid, Phenylacetic Acid Derivative
Mechanism Of Action	Blocks Voltage-Gated Sodium Channels In Neuronal Membranes To Inhibit Initiation And Conduction Of Nerve Impulses, Producing Local Anesthesia	Inhibits Cyclooxygenase (Primarily Cox-2 Preference Reported In Literature) To Reduce Prostaglandin Synthesis, Yielding Anti-Inflammatory And Analgesic Effects
Aqueous/Solvent Solubility	Sparingly Soluble In Water; More Soluble In Dilute Acids; Very Soluble In Ethanol, Chloroform, And Ether	Practically Insoluble In Water; Solubility Increases With Ph; Soluble In Some Organic Solvents; Uv Λmax ~275–276 Nm In Buffers For Assay
Melting Point	88–92 °C (Solid)	149–153 °C (Crystalline)
Logp (Octanol/Water)	~1.86 (Reported), 1.4–1.9 Range In Datasets	~3.9 (Calculated/Reported Range 3.5–4.0)
Therapeutic Use	Topical Anesthetic For Temporary Relief Of Pain/Itching Of Minor Skin/Mucosal Conditions (E.G., Oral, Dermal, Hemorrhoidal Preparations)	Management Of Osteoarthritis, Rheumatoid Arthritis, And Ankylosing Spondylitis; Analgesic And Anti-Inflammatory Therapy

Rationale For Combination Therapy :

Combining Benzocaine And Aceclofenac Into One Cream Offers A Superior, Synergistic Therapeutic Edge:

Dual Mechanism: Aceclofenac Simultaneously Targets And Lowers The Underlying Inflammation, While Benzocaine Instantly Stops The Nerve Signal. Quick Relief: While The Nsaid Action Offers Long-Lasting, Consistent Relief, The Local Anesthetic Provides Rapid Numbing. Decreased Systemic Toxicity: By Keeping The Medications Confined, Topical Usage Significantly Lowers The Chance Of Liver Strain Or Intestinal Irritation.

Formulation Development

Excipients, Emulsifiers, And Preparation Methods Must Be Carefully Chosen For A Cream To Be Successful. Since Aceclofenac And Benzocaine Are Both Fatsoluble (Lipophilic), We Favor An Oil-In-Water (O/W) Cream Base Due To Its Superior Stability And Ease Of Spreading.

1. Ingredients Used :

Ingredient	Role	Amount (G)	% W/W
Aceclofenac	Anti-Inflammatory Api	1.50	1.50%
Benzocaine	Local Anesthetic Api	10.00	10.00%
Carbopol 934p	Primary Gelling Polymer	0.80	0.80%
Hpmc K4m	Co-Gellant/Bioadhesion Enhancer	0.30	0.30%
Triethanolamine	Neutralizer/Ph Adjuster	0.35 (Q.S. To Ph 6.0–6.5)	0.35%
Polysorbate 80 (Tween 80)	Surfactant/Wetting Agent	1.00	1.00%
Peg-400	Cosolvent/Solubilizer	2.00	2.00%
Propylene Glycol	Humectant/Cosolvent	10.00	10.00%

9.2 Aceclofenac: Inhibition Of Prostaglandin Synthesis :

It Inhibits The Cyclooxygenase Enzymes That Produce Prostaglandins, Which Are Mediators Of Pain And Inflammation. This Immediately Lessens Swelling (Edema), Redness (Erythema), And Irritation.

9.3 Combined Action:

While Aceclofenac Works Longer And Deeper To Reduce The Underlying Inflammation, Benzocaine Provides The Patient With Immediate Pain Relief By Numbing The Affected Area. A Single Medication Cannot Equal The Increased Analgesic Potency Of This Combination.

1. Therapeutic Indications

. Localized Muscle Soreness And Stiffness Can Be Effectively Treated With This Dual-Action Cream. Inflammation Of The Joints (Such As Sprains Or Flare-Ups Of Arthritis). Pain And Neuralgia Following Small Surgeries. Mild Burns, Bug Bites, And Limited Tooth Pain.

1. Topical Combination Benefits:

The Topical Approach Delivers A Direct, Localized Analgesic And Anti-Inflammatory Activity That Improves Patient Outcomes While Avoiding The Serious Dangers Associated With Oral Nsaids.

Safety And Regulatory Considerations :
1. Toxicological Profile :

Although Benzocaine Is Usually Safe For Intact Skin, It Can Occasionally Cause Methemoglobinemia When Applied In Excess To Injured Skin Or Mucous Membranes. Low Dermal Toxicity Is Demonstrated By Aceclofenac. When Used Topically, Its Low Systemic Absorption Significantly Lowers The Likelihood Of Oral Nsaid Side Effects Such Inflammation. Combination Safety: Compared To Oral Methods, The Localized Application Guarantees A Far Lower Chance Of Major Systemic Adverse Effects.

1. Studies On Irritation And Sensitivity :

Clinical Testing Is Required To Verify Safety. To Make Sure The Cream Doesn't Produce Erythema (Redness), Irritation, Or Edema (Swelling), Patch Testing On Human Volunteers Is Essential. The Product's Suitability For Human Usage Is Confirmed By A Non-Irritating Reaction.

1. Regulatory Guidelines :

Who And Local Government Requirements For Topical Products Are Among The Regulatory Regulations That The Combo Cream Must Closely Follow. Ich Q1a(R2) Stability Testing Recommendations. Fda/Ema Labeling Regulations, Including Clear Cautions About The Local Anesthetic Component.

Storage And Packaging:

We Advise Storing The Completed Cream In Tight-Fitting, Collapsible Laminated Aluminum Tubes. Storage Should Be Kept Out Of Direct Sunlight And Moisture And Below 30 Degrees Celsius. Under These Circumstances, A Shelf Life Of About 24 Months Is Anticipated.

Future Prospects :

The Demand For Safe, Fastacting Topical Analgesics Is Growing, And This Cream Shows Great Potential For Innovation:

Enhanced Transdermal Systems: Future Research Should Focus On Incorporating The Drugs Into Advanced Carriers Like Liposomes, Niosomes, Or Nanoemulsions To Boost Skin Penetration And Target The Site Even Better.

Smart Gels: Developing Gels That Release The Drug Based On Local Cues, Such As Or Temperature Changes At The Site Of Inflammation, Offers Controlled And Sustained Therapy.

Personalized Formulations: Exploring 3d Printing To Create Customized Creams With Tailored Doses And Release Rates For Individual Pain Management Needs.

Further Clinical Trials Are The Next Step To Confirm Precise Bioavailability, Effectiveness, And Longterm Dermal Safety.

CONCLUSION:

The Topical Combination Of Benzocaine And Aceclofenac Offers An Effective, Dualaction Solution For Localized Pain And Inflammation Management. Benzocaine Provides Instant Relief By Blocking Nerve Signals, And Aceclofenac Ensures Sustained Antiinflammatory Action. By Formulating It As A Stable Oilinwater Cream, We Enhance Patient Compliance, Minimize Systemic Exposure, And Deliver Prolonged Therapeutic Benefit. This Benzocaine–Aceclofenac Cream Represents A Highly Promising Advancement In Modern Topical Analgesic Therapy.

REFERENCES

Rang, H. P., Ritter, J. M., Flower, R. J., & Henderson, G. (2016). Rang And Dale’s Pharmacology (8th Ed.). Elsevier
Sweetman, S. C. (Ed.). (2020). Martindale: The Complete Drug Reference (40th Ed.). Pharmaceutical Press.
Dashora, A., Chauhan, N., & Shrivastava, B. (2021). Formulation And Evaluation Of Aceclofenac Topical Gel. International Journal Of Pharmaceutical Sciences Review And Research, 68(1), 45–51.
Jain, A., & Gupta, Y. (2019). Formulation And Evaluation Of Topical Anesthetic Cream Containing Benzocaine. Asian Journal Of Pharmaceutics, 13(2), 123–128.
Indian Pharmacopoeia Commission. (2022). Indian Pharmacopoeia 2022 (Vol. I–Iii). Government Of India.
United States Pharmacopoeia (Usp). (2023). Usp–Nf Online. Rockville: Usp.
World Health Organization. (2023). Guidelines For Stability Testing Of Pharmaceutical Products. Who Press.
Shinde, P., & Kulkarni, S. (2020). Advances In Topical Drug Delivery Systems For Pain Management. Journal Of Drug Delivery And Therapeutics, 10(4), 120–128.
Salman, S., & Din, M. I. (2020). Benzocaine: Review On A Drug With Unfold Potential. Mini-Reviews In Medicinal Chemistry, 20(3), 3-11
Tej-Bahadur, N., Kumar, N., Gupta, A., & Gupta, R. K. (2022). A Critical Review On Aceclofenac Topical Nanoemulgel. Ijppr – International Journal Of Pharmaceutical & Phytopharmacological Research, 24(2), ... (Pages)
“Recent Advances In Topical Anesthesia.” (2016). Journal Of Dental Anesthesia And Pain Medicine, 16(4), 237-???
“Approach To Allergic Contact Dermatitis Caused By Topical Medicaments.” (2022). Dermatology/Contact Dermatitis Review, … (Volume)
“Formulation And In-Vitro Characterization Of Aceclofenac Emulgel.” (Date). Napdd – Nanotechnology And Advanced Pharmaceutical Drug Delivery, … (Pages)
“Formulation And Evaluation Of Topical Aceclofenac Gel Using Different Gelling Agent.” (2019). Journal Of Drug Delivery And Therapeutics, 9(5), 118-122.
“Efficacy Of Topical Anesthetics Of Lidocaine, Benzocaine, And Emla In Children.” (2024). Children, 12(5), 610.
“Benzocaine-Induced Methemoglobinemia: A Case Report.” (2016). Pmc Case Reports, … (Pages)
“Formulation Development And Evaluation Of Aceclofenac Sodium Gel.” (2015). Journal Of Chemical And Pharmaceutical Research, 7(10), 948-
Raza K, Kumar M, Kumar P, Malik R, Sharma G, Kaur M, Katare O. Topical Delivery Of Aceclofenac: Challenges And Promises Of Novel Drug Delivery Systems. Biomed Res Int. 2014;2014
Syeda Khair-Ul-Bariyah Et Al. Benzocaine: Review On A Drug With Unfold Potential. Mini-Reviews In Medicinal Chemistry. 2020;20(1).
Navarro-Rodriguez Jm, Suarez-Serrano C, Martin-Valero R, Marcen-Roman Y, De-La-Casa-Almeida M. Effectiveness Of Topical Anesthetics In Pain Management For Dermal Injuries: A Systematic Review. J Clin Med. 2021;10(11)
Estrella V, Sangalli L, Khan I, Fan J. Anesthesia In Periodontal Treatment: A Narrative Review Of Modalities And Advancements. J Oral Maxillofac Anesth. 2025;4:16.
Silva F, Costa G, Veiga F, Cardoso C, Paiva-Santos Ac. Parenteral Ready-To-Use Fixed-Dose Combinations Including Nsaids With Paracetamol Or Metamizole For Multimodal Analgesia — Approved Products And Challenges. Pharmaceuticals. 2023;16(8):1084.
Saud N. Aldanyowi. Novel Techniques For Musculoskeletal Pain Management After Orthopedic Surgical Procedures: A Systematic Review. Life. 2023;13(12):2351.
Metavee Boonsiri, Katherine C. Marks, Chérie M. Ditre. Benzocaine/Lidocaine/Tetracaine Cream Report Of Corneal Damage And Review. J Clin Aesth Dermatol. (Date).
Post-Operative Analgesic Effects Of Paracetamol, Nsaids, Glucocorticoids, Gabapentinoids And Their Combinations: A Topical Review. (2014)
Sandeep Ds. Development, Characterisation, And In Vitro Evaluation Of Aceclofenac Emulgel. Asian J Pharmaceutics. 2020;14(03).