Adsorption Studies of Bromhexine Hydrochloride on Talc

 

Namdeo R. Jadhav¹*, Anant R. Paradkar², Gourav N. Shah¹

¹Department of Pharmaceutics, Bharati Vidyapeeth College of Pharmacy, Kolhapur-416013, Maharashtra, India.

²Institute of Pharmaceutical Innovation, University of Bradford, UK

*Corresponding Author E-mail: nrjadhav18@rediffmail.com

 

The objective of the present work was to study the adsorption of bromhexine hydrochloride (BXH)on talc, since it has been used in design of spherical agglomerates. The adsorption study was performed taking talc and binary solvent system comprising methanol: water (15%: 85% Vol/Vol; 20%: 80% Vol/Vol; 25%: 75% Vol/Vol). Therein, BXH drug was added with increasing concentrations 50, 100, 150, 200, 250 and 300 µg/ml. The adsorped drug was filtered, centrifuged and supernatant/filtrate was checked for absorbance at λ_max 317nm. It was found that BXH was adsorbed on the talc particles due to poor solubility of BXH in water, and hydrophobicity of talc. This has been confirmed by regression analysis. The adsorption study perfoedm by Langmuir and Freundlich adsorption isotherms showed statistical difference between ‘A’ and ‘a’(P<0.05). The increased in monolayer capacity with methanol concentration has also been noted.  However, the drug adsorption is least, hence, talc can be considered as as a diluent, on whom, least drug adsorption is noted and secondly its physicochemical and physiological inertness along with inexpensive nature reinforces its application in design of novel dosage forms like pellets etc.

 

INTRODUCTION:

Adsorption properties of drug have become an important tool in designing ER and SR drug delivery system. There are lots of excipients which shows the adsorption of drug which affect the drug release. Adsorption is the phenomenon by which the molecules of the gas/vapor or liquid get concentrated at the contacting surface by undergoing the physical or chemical interaction.^1,2

 

The talc fulfills all the criteria of the diluent, viz: non toxic, physiologically inert, hydrophobic, inexpensive and abundantly found nature. So the utility of talc in the dosage form design varies with its percentage used. By taking into account this property of talc we attempted to use talc in the process of CCA and WSA.³ The crystallo-co-agglomeration technique is related to the particle engineering in which BXH-talc agglomerates prepared by crystallo-co-agglomeration they found that the tensile strength of the compact is increased and which is responsible for the extended release of BXH from compact. Here adsorption of drugs on the talc is not considered which have an effect on the drug release.

 

This possibility was also found in other literatures also.⁴ We found there is adsorption of the BXH in the agglomerates.^5,6 The further research survey found  that agglomerates of talc-Ibuprofen and talc-Paracetamol which are prepared by CCA are also associated with the talc-drug adsorption  properties.^7,8

 

Research finding on in vitro studies on the adsorption of various drugs on talc quotes least adsorption capacity as compared to the adsorbents like kaolin activated charcoal, magnesium trisilicate etc. Drugs evaluated in the adsorption studies were Calcium, diazepam.⁹ A range of antibiotics like metformin hydrochloride, glibenclamide, acetohexamide, tolbutamide, glymidine and carbutamide¹⁰ had significantly low adsorption on talc as compared to the others.Virtually nonexistent adsorption was seen on magnesium hydroxide, aluminum hydroxide and magnesium trisilicate. Amongst the rest of adsorbents, talc had the lowest adsorption capacity.¹¹

 

The rapid dissolution of drugs by the rapid dissipation from the adsorbent surface of silica type of compounds has been attributed to hydrogen bonding and van der Waals forces.¹² So the adsorption of the drug by the talc would facilitate the drug dissolution rate and the desorption will allow the full availability of the drug. It has been reported that salicylic acid was released in vitro at a faster rate in the presence of talc compared to stearate.¹³ Thus  hydrophobic lubricants retard the dissolution of the drugs present in the compressed tablets by prolonging the disintegration time and reducing the area of the interface between the drug particle and solvent. The presence of the adsorbent increasing the dissolution by increasing the apparent saturation concentration of the drug.¹⁴

 

There are various problems regarding with the adsorption of drug on talc of different drugs specially drugs with low dose. There is a need of work to study the effect of absorption of drugs on talc because various types of adsorption work were performed on different drug-excipient adsorption to study the drug release pattern but yet adsorption study work is not performed on the BXH and there is a must need of study it to understand  the actual adsorption strength of  talc with drug with their adsorption studies.

 

MATERIALS AND METHODS:

Materials:

Bromhexine hydrochloride (BXH) was a gift from IPCA Laboratories Ltd (Mumbai, India). Talc (Indian Pharmacopoeia grade) was supplied by Get-Rid Pharma (Pune, India). Methanol and all other chemicals were of analytical grade.

 

Experimental Methods:

Adsorption of BXH on talc was studied in water, and methanol water binary solvent system. 50, 100, 150, 200, 250 and 300 µg/ml concentrations of BXH were made from stock solution prepared with water, and methanol: water binary system (15%: 85% Vol/Vol; 20%: 80 Vol/Vol; 25%: 75 Vol/Vol). The volume was adjusted to 100mL with the same solvent system used. To each solution of BXH having different concentrations, 0.5 g of talc was added and equilibrated for 1 hour at 25±2⁰C. After equilibrium has attained, the whole slurry was filtered, centrifuged, and the supernatant was filtered through Whatman filter paper no 42 and the filtrate was analyzed by UV-Visible spectrophotometer at λ max for the corresponding solvent system separately. The filtrate was analyzed spectrophotometrically at 317 nm (Shimadzu 160, Kyoto, Japan) (Table No.1). The values of the slope and constant obtained from the standard curve of BXH in the respective solvent systems were used for the determination of free drug which has got adsorbed on talc (Table No.2). Content of unbound BXH was determined from standard curve using values of regression coefficients.^{15, 16} The amount of drug adsorbed by talc were used to calculate monolayer adsorption capacity of talc (Table No.3).

 

The adsorption BXH was studied by the Langmuir and Freundlich adsorption isotherms¹⁷ as given by following equations,

 

Langmuir Isotherm:

	Eq.1

 

Where, ‘Vads’ is the volume of gas adsorbed per mass of adsorbate at ‘P’, ‘P’ is the vapor pressure of adsorbate gas. ‘Vm’ is the volume of absorbent at full monolayer coverage, and ‘a’ as a constant dependant on temperature.

 

Freundlich Adsorption Isotherm:

 

Where, ‘X’ is mass of gas adsorbed per unit mass ‘m’ of the adsorbent and ‘P’ is the equilibrium pressure of the gas in mm of Hg, where, ‘k’ and ‘n’ are constants.

 

RESULTS AND DISCUSSION:

The utility of talc in the dosage form design varies with its percentage used. It fulfills all the criteria of the diluent, viz: non toxic, physiologically inert and inexpensive nature.

Present studies on the adsorption of BXH on talc in different solvents, has shown that in water 0.3 g of BXH has been adsorbed per g of talc. This has been because of poor solubility of BXH in water, which might have got reduced at ambient temperature. But in case of solvent system composed of methanol and water, increased adsorption has been seen. It was maximum at methanol: water (15:85) composed. But it has been observed that, with the increase in amount of methanol in binary solvent system leads to a reduction in the adsorption capacity of talc (Table 2). Rather from the Figure 1, it has been evident that after certain concentration of BXH, the amount of disruption has been promoted due to increase in the amount of methanol in the binary system. This might have been due to more affinity of BXH for methanol than talc. And the difference between the values of adsorption capacity (A) for all four solvent systems was statistically significant at p<0.05.

 

The values of regression analysis obtained from the standard curve of BXH concentration and observance in different solvent systems have been given in Table 2. Present studies on the adsorption of BXH on talc in different solvents, has shown that, in water 0.3 g of BXH has been adsorbed per g of talc. This has been because of poor solubility of BXH in water. But in case of solvent system composed of methanol and water (methanol is a good solvent for methanol), increased adsorption has been seen. It was the maximum in methanol: water (15:85) composition. But it has been observed that, with the increase in amount of methanol in binary solvent system leads to a reduction in the adsorption capacity of talc (Table 2). The difference between the values of adsorption capacity (A) of talc in all four solvent systems was statistically significant at p<0.05. This has been seen due to changes in the affinity of BXH towards solvent systems having different composition.

 

Monolayer capatity was calculated from the obtained information from table no.1 and 2 by using formula. The observations shows that as concentration of methanol increases in the binery system

 

Table 1. Regression Analysis Constants for Standard Curves of Concentration of BXH versus Absorbance in Water, and Methanol Water Binary Solvent System at λ_max 317 nm.

 

Fig 1: Graphs of Langmuir and Freundlich adsorption isotherm of BXH and Talc at various concentrations of methanol and water binery system

Table 2.Constants for Langmuir and Freundlich Adsorption Isotherm for Adsorption of BXH to Talc*^18,19

Solvent system	Langmuir			Freundlich
	A	C	R2	a	C	r2
Water**	0.363±0.0259	9.115±0.129	0.703±0.012	1.145±0.097	0.734±0.142	0.607±0.087
MeOH:H2O (15:85)**	0.959±0.071	3.575±0.0.98	0.821±0.059	2.501±0.125	0.751±0.125	0.658±0.100
MeOH:H2O (20:80) **	0.793±0.048	4.695±0.158	0.157±0023	1.151±0.092	0.331±0.055	0.504±0.154
MeOH:H2O (25:75)**	0.476±0.054	-.096±0.0201	0.352±0.025	0.527±0.055	-0.724±0.058	0.745±0.078

*A, C, R² indicates slope, constant and correlation coefficient for Langmuir adsorption isotherm and a, c, r² for Freundlich adsorption isotherm respectively. **Statistically significant difference between A and a at P<0.05

 

 

Table 3.Monolayer adsorption capacity for Langmuir and Freundlich Adsorption Isotherm for Adsorption of BXH to Talc:

 

CONCLUSION:

Talc being inert and inexpensive, has been widely used traditionally in pharmaceutical formulations. However, recently, its role as a pellet exceipient and hydrophobic diluent has been established. The studies have confirmed least adsorption of BXH on talc. Thus, the findings support its role as a old excipient with new use in design of novel dosage forms.

 

ACKNOWLEDGEMENT:

We are extremely thankful to Dr. H. N. More, Principal, Bharati Vidyapeeth College of Pharmacy, Kolhapur for providing excellent facilities to carry out this work.

 

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Accepted on 08.10.2013      © RJPT All right reserved