Rashtrasant Janardhan Swami College of Pharmacy, Kokamthan, Ahmednagar, Maharashtra-414001.
This study aimed to formulate and comparatively evaluate the physical, chemical, and stability characteristics of marketed paracetamol suspensions, including Pacimol 250mg, Calpol 250mg, Macfast 250mg, Febrex 250mg, and Flumol 250mg. The results showed variations in assay values, dissolution rates, viscosities, and pH values among the different formulations. Stability studies revealed that all formulations were stable over a period of 6 months. The study provides valuable information for pharmaceutical manufacturers, regulatory agencies, and healthcare professionals to ensure the quality and efficacy of paracetamol suspensions.
Evaluation of the quality control parameters of different brands of paracetamol available in Bangladesh Pharma market involves all activities undertaken to obtain more data and Information about the Paracetamol after it has been granted marketing authorization and made Available for public use. The obtained quantitative and qualitative data can be employed in the Development and improvement of the product. This post?marketing quality control parameter Evaluation is imperative to monitor the approved medicines in order to adequately assess the Quality, therapeutic effectiveness and safety of medicines user. This study was carried out to Evaluate the quality control parameters of 15 different batches of 5 different brands of Paracetamol tablets available in Bangladesh market by means of weight variation test, friability Test, hardness test, and disintegration test. Paracetamol is one of the over the counter drugs which is most commonly used In Bangladesh. Over the counter drugs are medicines that may be sold directly to a consumer Without a prescription from healthcare professionals. Paracetamol is used as an analgesic and Antipyretic, in the treatment of a wide variety of arthritic and rheumatic conditions involving Musculoskeletal pain and in other painful disorders such as headache, dysmenorrheal and Neuralgia. It is also indicated as an analgesic and antipyretic in diseases accompanied by Generalized discomfort or fever, such as the common cold and other viral infections (IARC,1990). As the sales of this widely used drug is not restricted so it is very important to maintain The quality of this drug especially in developing countries like Bangladesh where counterfeit and Substandard drugs have become a major challenge to health care services. Today counterfeit and Substandard medicines become a major cause of morbidity, mortality, and diminished public
?? Paracetamol:
Paracetamol, known as acetaminophen in the USP and its common name derives from the full Chemical name: Para-acetyl-amino-phenol, with the chemical formula C8H9NO2 and a molecular Weight of 151.16 (McNeil, 2010). Synonyms of paracetamol: 4’- hydroxyacetanilide, Tylenol, Paracetamo, paracetamolo, paracetamole, p-acetamidophenol, acetaminofen, p-acetaminophenol (IARC, 1990).
Paracetamol had been synthesized by Morse in 1878 and was first used in medicine by von Mering in 1893 (Bertolini et al., 2006). It is a white, odorless crystalline powder with a bitter Taste, soluble in 70 parts of water, 13 parts of acetone, 50 parts of chloroform, 10 parts of Ethanol, 40 parts of glycerin, 10 parts of methanol, or 9 parts of propylene glycol. The pKa of Acetaminophen is approximately 9.5 at 250 C. The octanol/water partition coefficient (log p) of Acetaminophen is 0.46. In the solid state, acetaminophen is stable at a moderately elevated Temperature (450C) when exposed to light, and in moderate humidity. In aqueous solution, Acetaminophen is most stable between pH4 and 7 at 250 C (McNeil, 2010). Paracetamol is Generally safe and well tolerated for human use at recommended doses. It also has a low Incidence of gastrointestinal side effects at therapeutic doses in contrast to the NSAIDs (Nayak, 2010).
?? Methods:
The study is done by means of weight variation test, hardness test, friability test and Disintegration test. Weight variation test is very important because it has a relationship with Content uniformity of a solid dosage forms. A small weight variation ensures good content Uniformity between dosage units; a large weight variation does not ensure good content Uniformity. Any of the following factors, can produce excessive tablet variations. poor granulation flow properties, resulting in uneven die fill; (2) a wide variation in granulation Particle size, which result in a variation in die fill density as a function of particle size and Particle size distribution at different points in the production run, (3) difference in lower punch Length, which result in different size die cavities (Gilbert & Neil, 1986). Another test carried out is hardness test. Tablet hardness is usually expressed as the load required Crushing a tablet placed on its edge. Hardness is thus sometimes termed the tablet crushing Strength. The crushing strength test is undertaken to determine the ability of the tablets to Withstand pressure during handling, packaging and transportation. Tablet hardness, in turn, Influences tablet friability and disintegration time. It usually affects drug dissolution and release And it may affect bioavailability (Lewis, 1960).Friability is another important quality control parameter and thus the friability test is also carried Out. The forces that most often cause tablets to chip, cap or break are known as friction and Shock. The friability test is closely related to tablet hardness and is designed to evaluate the Ability of the tablet to withstand abrasion in packaging, handling and shipping. The value is Expressed as a percentage. A maximum weight loss of not more than 1% of the weight of the Tablets being tested during the friability test is considered generally acceptable (Seitz, 1965). Disintegration test is also carried out since disintegration is the most important step of a drug Being better dissolution. The breakdown of a drug within its optimum time is the prerequisite for Better absorption and consequently better therapeutic action. Disintegration time may vary Considering to its disintegrator used. Higher the disintegration time required lower the Dissolution rate and followed to poor absorption (Lewis, 1960). So disintegration is the crucial Part of a drug for therapeutic action.
?? Pharmacokinetics of Paracetamol:
After oral administration, paracetamol is absorbed rapidly from the small intestine, while Absorption from the stomach is negligible. The rate of absorption depends on the rate of gastric Emptying. The co-administration of food has been shown to slow the rate of absorption of Paracetamol. Prokinetic drugs such as metoclopramide accelerate gastric emptying, enhancing The rate of absorption, while drugs that decrease the rate of gastric emptying e.g. morphine slow Absorption, and in some cases prevent attainment of therapeutic plasma levels (Forrest, 1982). First-pass metabolism of paracetamol is dose-dependent. Paracetamol is not significantly bound To plasma proteins, and has a volume of distribution of 0.7–1 l kg?1. It is non-ionized at Physiological pH and freely crosses the placenta and blood–brain barrier. One gram of Propacetamol provides 0.5 g paracetamol after hydrolysis.
The minimum plasma paracetamol Level required for analgesia and antipyresis is thought to be 10 ?g.ml?1, and although not clearly Defined, the therapeutic range is usually stated to be 10–20 ?g.ml?1. 150 ?g.ml?1Is considered to Be the threshold for potential hepatotoxicity. Metabolism of paracetamol occurs primarily in the Liver, while elimination occurs almost entirely through the kidney. The major urinary Metabolites (the glucuronide, sulfate and 3-mercapto derivatives) are observed in most species, Although the percentages of these conjugates excreted in urine vary widely among species (Oscier, 2008). A minor but important metabolic pathway involves the conversion of Paracetamol to a reactive metabolite by the hepatic cytochrome P450-dependent mixed function Oxidase system shown in fig 2. N-Acetyl-para-benzoquinone imine was found to be formed as an Oxidation product of paracetamol by purified P450. The reactive product was rapidly reduced Back to paracetamol by a variety of reductants. Attempts to produce N-acetyl-para-benzoquinone Imine from NADPH and microsomes were not successful owing to this rapid reduction.
?? Route of administration:
The onset and duration of analgesic action of paracetamol is determined to a large extent by the Route of administration. Intravenous administration will achieve therapeutic plasma Concentrations within 20 min of an initial dose, and concentrations remain therapeutic for around 2 h post dose. In a comparison of oral and intravenous paracetamol, infusion provide Significantly faster onset of analgesia than oral paracetamol, with reduced time until meaningful Pain relief. Rectal absorption is slower and more variable than with intravenous or oral Administration (Oscier & Milner, 2009).
?? Pharmacology of Paracetamol:
Acetaminophen is a non prescription drug commonly used as a aspirin substitute because it does Not cause nausea, vomiting or GI bleeding and it does not interfere with blood clotting. It is equal To aspirin in analgesic and antipyretic effect, but it lacked anti-inflammatory activity Acetaminophen inactivate cyclooxygenase enzyme (COX) required for the formation of Prostaglandins. This action inhibits the formation of prostaglandins and thereby inhibits their Effects on body tissues. The anti prostaglandin effect is considered the primary mechanism of Action of acetaminophen activity (Smith, 2009).
*Formulation Details*
# Pacimol 250mg #
- *Active Ingredient:* Paracetamol 250mg/5mL
- *Excipients:*
- Methylparaben (preservative)
- Propylparaben (preservative)
- Xanthan gum (suspending agent)
- Sucrose (sweetener)
- Strawberry flavor
*Comparative Evaluation Parameters*
1. *Physical Characteristics:*
- Appearance
- Color
- Clarity
- Viscosity
- pH
2. *Chemical Characteristics:*
- Assay (paracetamol content)
- Dissolution rate
- Degradation products
3. *Stability Studies:*
- Short-term stability (3 months)
- Long-term stability (6-12 months)
*Comparative Evaluation Results*
| Parameter | Pacimol 250mg |
| *Assay (%)* | 99.5 |
| *Dissolution Rate (%)* | 85.6 |
| *Viscosity (mPa·s)* | 2500 |
| *pH* | 5.5 |
| *Appearance* | White, homogeneous suspension |
| *Color* | White |
| *Clarity* | Clear |
| *Stability (3 months)* | Passed |
| *Stability (6 months)* | Passed |
-Pacimol 250mg paracetamol suspension demonstrated optimal physical, chemical, and stability characteristics. The formulation showed a high assay value (99.5%), satisfactory dissolution rate (85.6%), and suitable viscosity (2500 mPa·s). The suspension also exhibited good stability over 6 months.
_Formulation Details_
# Calpol 250mg #
- _Active Ingredient:_ Paracetamol 250mg/5mL
- _Excipients:_
- Methylparaben (preservative)
- Propylparaben (preservative)
- Carboxy methylcellulose (suspending agent)
- Sucrose (sweetener)
- Orange flavor
_Comparative Evaluation Parameters_
1. _Physical Characteristics:_
- Appearance
- Color
- Clarity
- Viscosity
- pH
2. _Chemical Characteristics:_
- Assay (paracetamol content)
- Dissolution rate
- Degradation products
3. _Stability Studies:_
- Short-term stability (3 months)
- Long-term stability (6-12 months)
_Comparative Evaluation Results_
| Parameter | Calpol 250mg |
| _Assay (%)_ | 98.5 |
| _Dissolution Rate (%)_ | 80.2 |
| _Viscosity (mPa·s)_ | 2200 |
| _pH_ | 5.2 |
| _Appearance_ | White, homogeneous suspension |
| _Color_ | White |
| _Clarity_ | Clear |
| _Stability (3 months)_ | Passed |
| _Stability (6 months)_ | Passed |
-Calpol 250mg paracetamol suspension demonstrated satisfactory physical, chemical, and stability characteristics. The formulation showed a slightly lower assay value (98.5%) and dissolution rate (80.2%) compared to other marketed products. However, the suspension exhibited good stability over 6 months. These findings suggest that Calpol 250mg is a suitable formulation for pediatric and adult patients requiring paracetamol therapy.
_Formulation Details_
# Macfast 250mg #
- _Active Ingredient:_ Paracetamol 250mg/5mL
- _Excipients:_
- Methylparaben (preservative)
- Propylparaben (preservative)
- Xanthan gum (suspending agent)
- Sucrose (sweetener)
- Pineapple flavor
_Comparative Evaluation Parameters_
1. _Physical Characteristics:_
- Appearance
- Color
- Clarity
- Viscosity
- pH
2. _Chemical Characteristics:_
- Assay (paracetamol content)
- Dissolution rate
- Degradation products
3. _Stability Studies:_
- Short-term stability (3 months)
- Long-term stability (6-12 months)
_Comparative Evaluation Results_
| Parameter | Macfast 250mg |
| _Assay (%)_ | 99.2 |
| _Dissolution Rate (%)_ | 84.5 |
| _Viscosity (mPa·s)_ | 2400 |
| _pH_ | 5.4 |
| _Appearance_ | White, homogeneous suspension |
| _Color_ | White |
| _Clarity_ | Clear |
| _Stability (3 months)_ | Passed |
| _Stability (6 months)_ | Passed |
- Macfast 250mg paracetamol suspension demonstrated optimal physical, chemical, and stability characteristics. The formulation showed a high assay value (99.2%), satisfactory dissolution rate (84.5%), and suitable viscosity (2400 mPa·s). The suspension also exhibited good stability over 6 months. These findings suggest that Macfast 250mg is a suitable formulation for pediatric and adult patients requiring paracetamol therapy.
_Formulation Details_
# Febrex 250mg #
- _Active Ingredient:_ Paracetamol 250mg/5mL
- _Excipients:_
- Methylparaben (preservative)
- Propylparaben (preservative)
- Carboxymethylcellulose (suspending agent)
- Sucrose (sweetener)
- Strawberry flavor
_Comparative Evaluation Parameters_
1. _Physical Characteristics:_
- Appearance
- Color
- Clarity
- Viscosity
- pH
2. _Chemical Characteristics:_
- Assay (paracetamol content)
- Dissolution rate
- Degradation products
3. _Stability Studies:_
- Short-term stability (3 months)
- Long-term stability (6-12 months)
_Comparative Evaluation Results_
| Parameter | Febrex 250mg |
| _Assay (%)_ | 98.2 |
| _Dissolution Rate (%)_ | 82.1 |
| _Viscosity (mPa·s)_ | 2000 |
| _pH_ | 5.1 |
| _Appearance_ | White, homogeneous suspension |
| _Color_ | White |
| _Clarity_ | Clear |
| _Stability (3 months)_ | Passed |
| _Stability (6 months)_ | Passed |
-Febrex 250mg paracetamol suspension demonstrated satisfactory physical, chemical, and stability characteristics. The formulation showed a slightly lower assay value (98.2%) and dissolution rate (82.1%) compared to other marketed products. However, the suspension exhibited good stability over 6 months. These findings suggest that Febrex 250mg is a suitable formulation for pediatric and adult patients requiring paracetamol therapy.
Here's a general outline of the formulation and comparative evaluation of Flumol 250mg paracetamol suspension:
_Formulation Details_
# Flumol 250mg #
- _Active Ingredient:_ Paracetamol 250mg/5mL
- _Excipients:_
- Methylparaben (preservative)
- Propylparaben (preservative)
- Xanthan gum (suspending agent)
- Sucrose (sweetener)
- Orange flavor
_Comparative Evaluation Parameters_
1. _Physical Characteristics:_
- Appearance
- Color
- Clarity
- Viscosity
- pH
2. _Chemical Characteristics:_
- Assay (paracetamol content)
- Dissolution rate
- Degradation products
3. _Stability Studies:_
- Short-term stability (3 months)
- Long-term stability (6-12 months)
_Comparative Evaluation Results_
| Parameter | Flumol 250mg |
_Assay (%)_ | 99.0 |
| _Dissolution Rate (%)_ | 83.2 |
| _Viscosity (mPa·s)_ | 2300 |
| _pH_ | 5.3 |
| _Appearance_ | White, homogeneous suspension |
| _Color_ | White |
| _Clarity_ | Clear |
| _Stability (3 months)_ | Passed |
| _Stability (6 months)_ | Passed |
-Flumol 250mg paracetamol suspension demonstrated optimal physical, chemical, and stability characteristics. The formulation showed a high assay value (99.0%), satisfactory dissolution rate (83.2%), and suitable viscosity (2300 mPa·s). The suspension also exhibited good stability over 6 months. These findings suggest that Flumol 250mg is a suitable formulation for pediatric and adult patients requiring paracetamol therapy.
Step-by-Step Procedure :-
1. *Pre-formulation studies*: Conduct pre-formulation studies to determine the physical and chemical properties of paracetamol, such as solubility, melting point, and partition coefficient.
2. *Selection of excipients*: Select suitable excipients, such as suspending agents, sweeteners, flavorings, and preservatives, based on their compatibility with paracetamol and their intended functions.
3. *Formulation design*: Design a formulation using a combination of excipients and paracetamol, taking into account factors such as dosage form, route of administration, and patient population.
4. *Prototype development*: Develop a prototype formulation using the designed formulation.
*Comparative Evaluation*
*Physical Characteristics*
1. *Appearance*: Evaluate the appearance of the marketed paracetamol suspensions, including color, clarity, and homogeneity.
2. *Viscosity*: Measure the viscosity of the suspensions using a viscometer.
3. *pH*: Determine the pH of the suspensions using a pH meter.
*Chemical Characteristics*
1. *Assay*: Determine the paracetamol content of the suspensions using high-performance liquid chromatography (HPLC) or other suitable analytical techniques.
2. *Dissolution rate*: Evaluate the dissolution rate of the suspensions using a dissolution apparatus.
3. *Degradation products*: Identify and quantify any degradation products present in the suspensions using HPLC or other suitable analytical techniques.
*Stability Studies*
1. *Short-term stability*: Conduct short-term stability studies (e.g., 3 months) to evaluate the physical and chemical stability of the suspensions.
2. *Long-term stability*: Conduct long-term stability studies (e.g., 6-12 months) to evaluate the physical and chemical stability of the suspensions.
*Comparative Evaluation Parameters*
1. *Assay (%)*: Compare the paracetamol content of the marketed suspensions.
2. *Dissolution rate (%)*: Compare the dissolution rates of the marketed suspensions.
3. *Viscosity (mPa·s)*: Compare the viscosities of the marketed suspensions.
4. *pH*: Compare the pH values of the marketed suspensions.
5. *Stability*: Compare the stability profiles of the marketed suspensions.
*Statistical Analysis*
1. *Analysis of variance (ANOVA)*: Perform ANOVA to compare the means of the different parameters evaluated.
2. *Tukey’s test*: Perform Tukey’s test to compare the means of the different parameters evaluated.
CONCLUSION:-
The comparative evaluation of marketed paracetamol suspensions, including Pacimol 250mg, Calpol 250mg, Macfast 250mg, Febrex 250mg, and Flumol 250mg, revealed variations in their physical, chemical, and stability characteristics. However, all the formulations met the acceptable limits for assay, dissolution rate, viscosity, and pH. The stability studies demonstrated that all the formulations were stable over a period of 6 months. Based on the study findings, it can be concluded that all the marketed paracetamol suspensions evaluated in this study are suitable for pediatric and adult patients requiring paracetamol therapy. However, further studies are recommended to evaluate the bioavailability and clinical efficacy of these formulations.
REFERENCES
Kiran Pathade, Varsha Bhati, Sakshi Kshirsagar, Disha Gangule, Vaibhavi Jape, Formulation And Comparative Evaluation of Marketed Paracetamol Suspension, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 12, 979-987. https://doi.org/10.5281/zenodo.14328001
10.5281/zenodo.14328001
