Analytical Method Development for Phenylpropanolamine Hydrochloride Sustained Release Pellets

 

Rakhee K Kotecha¹*, Anand S Surana², AV Chandewar¹, PD Nakhat³, and NP Jogad⁴

¹Department of Pharmaceutics, P.W. College of Pharmacy, Yavatmal, Maharashtra, India.

²Department of Pharmacology, S.K.B College of Pharmacy, Kamptee, Maharashtra, India.

³Pharma Research, Wochardt Research Centre, Aurangabad, India.

⁴Formulation and Development, Inventia Health Care Pvt. Ltd., Thane, India.

*Corresponding Author E-mail: rakhi_kotecha@yahoo.com

ABSTRACT:

The main aim of the present study was to developed analytical method for phenylpropanolamine hydrochloride (PPH) in PPH sustained release pellets. Analysis of PPH i.e. assays and dissolution has been given in USP by HPLC method. No UV-Visible spectrometry method has been reported for the analysis of PPH. Analysis of PPH was carried out by using UV-Visible spectrometry after performing the part method validation of specificity (scanning the standard solution of PPH), filter paper validation and linearity. Sustained release pellets were fabricated containing PPH by solution/suspension layering technique. A solution of PPH was prepared in distilled water and UV spectrum was taken using Perkin Elmer, Lambda25- UV/Vis Spectrophotometer. Filter paper validation was done by filtering standard PPH solution (10ppm) through Whatman filter paper No. 41 and absorbances of filtered solution was taken repetitively and compared with unfiltered solution at 205 nm. There was negligible changed in absorbance was obtained. The data for calibration plot showed good linear graph with r2 = 0.9980 for PPH. According to international conference on harmonization (ICH) guidelines, the present method was validated for precision, repeatability and recovery.

 

 

 

1.   INTRODUCTION:

Phenylpropanolamine hydrochloride (Molecular formula: C₉H₁₃NO.HCl; Molecular weight: 187.7); (1S, 2R)-2-amino-1-phenylpropan-1-ol hydrochloride) is a non-prescription sympathomimetic agent. The literature survey revealed that Phenylpropanolamine (PPA) is structurally similar to pseudoephedrine and is used to treat nasal congestion.¹ It is frequently used in combination preparations for the relief of cough and cold symptoms. It is one of few OTC products available also as an appetite suppressant to promote weight loss.² It is a water soluble drug with bioavailability about 38% and plasma half-life is about 2.1-3.4 hours (3.9 hours).^{1, 3} Phenylpropanolamine act as vasoconstrictors, diminishing blood flow into the capillary bed of the mucosa and reducing blood volume in the mucosal capacitance vessels (sinusoids) by their direct and indirect action on the alpha-1 and alpha-2 adrenergic receptors.^{4- 6} Analysis of PPH i.e. assay and dissolution has been given in USP by HPLC method.⁷ No UV-Visible spectrometry method was available for the analysis of PPH.

 

Analysis of Phenylpropanolamine hydrochloride was carried out by using UV-Visible spectrometry after performing the part method validation of specificity (scanning the standard solution of PPH), filter paper validation and linearity. The method described is simple, fast, precise and accurate for determination of PPH in PPH sustained release pellets.

 

2. MATERIALS AND METHODS:

2.1. Materials:

Phenylpropanolamine hydrochloride (Powder, Neha Pharma, India), hypromellose E5 (Dow Chemicals, Tokyo, Japan), ethylcellulose 10 cps (Dow Chemical, Tokyo, Japan),  ethylcellulose 45 cps (Colorcon Asia Pvt. Ltd., USA), and povidone K30 (ISP), colloidal silicon dioxide / Aerosil 200 (Degussa), dibutyl sebacate (Vertellus, France), isopropyl alcohol (Lee Chang, China), acetone (Mumbai Chemical, India), methanol (Merck, Germany), methylene chloride (Qualigen Fine Chemicals, India) and nonpareil seeds 18-20# (Oros Labs Pvt. Ltd, Thane, India).

 

2.2. Equipments:

Uni Glatt Fluid Bed Processor (Glatt, Germany) was used for drug solution layering and also for sustained release coating. Dissolution tester (Electrolab, India) and Lambda25 -UV/Vis spectrometer (Perkin Elmer) were used to study drug release profile. All dilutions were performed in standard volumetric flasks.

 

2.3. Working standard solution preparation:

100 mg of phenylpropanolamine Hydrochloride was taken in a 100 mL volumetric flask. This was dissolved in minimum quantity distilled water and sonicated for 15 minutes or till it was completely dissolved and diluted up to the mark to get a concentration 1000 μg/mL of phenylpropanolamine hydrochloride. Then 1ml of above solution was diluted with distilled water up to 100ml to get a concentration 10 μg/mL.

 

2.4. Sample solution preparation:

Twenty capsules were weighed and average weight of pellets was calculated. These pallets were powdered. Weighed equivalent to one capsule was taken in a 100 mL volumetric flask; dissolved in minimum amount distilled water and sonicated for 30 minutes and was diluted up to the mark with distilled water. That solution was then filtered through Whatman’s filer paper no. 41 and the filtrate was collected in the flask. Two mL of that filtrate was diluted to 100 mL with distilled water to get 10.00 μg/mL of Phenylpropanolamine hydrochloride.

 

2.4. UV-Spectrum:

A solution of phenylpropanolamine hydrochloride (10 μg/mL) was prepared in distilled water and UV spectrum was taken using Perkin Elmer, Lambda25- UV/Vis Spectrophotometer. UV-Spectrum of PPH was shown in Fig.1.

 

Fig. 1: UV Spectrum of Phenylpropanolamine Hydrochloride

 

2.5. Optimized UV-Operating Conditions:

UV Detection:                                    205 nm

Media:                                                 Distilled Water

Slit Width:                                          1 nm

Cycle count:                                        1

Cycle time:                                          1 sec

Lamp change-over wavelength:          326nm

 

2.6. Calibration curve of phenylpropanolamine hydrochloride:

100mg of phenylpropanolamine hydrochloride was weighed accurately and transferred into 100ml volumetric flask. It was dissolved and diluted with distilled water to give a stock solution containing 1000µg/ml. The standard stock solution was then serially diluted with distilled water to get 1, 3, 5, 10, 12.5, 15, and 20 µg/mL of phenylpropanolamine hydrochloride. The absorbances of the solution were measured against distilled water as blank at 205 nm using UV spectrophotometer. The absorbance values (Table 1) were plotted against concentration (µg/ml) to obtain the standard calibration curve as shown in Fig.2.

 

Table 1

Sr. No.	Concentration (ppm)	Absorbance	Average Absorbance
1.	0	0.0000	0.0000
		0.0000
2.	1	0.0344	0.0333
		0.0322
3.	3	0.1254	0.1251
		0.1247
4.	5	0.1854	0.1850
		0.1846
5.	10	0.4386	0.4363
		0.4339
6.	12.5	0.5394	0.5403
		0.5412
7.	15	0.6546	0.6505
		0.6464
8.	20	0.8584	0.8569
		0.8554

 

Fig. 2: Calibration Curve of PPH

 

2.7. Filter paper validation:

Standard solution of PPH (10ppm) was prepared and absorbance was taken at 205 nm. Standard solution was filtered through Whatman filter paper No. 41 (1^st filtration) and absorbance was taken at 205 nm. Then again standard solution was filtered through same Whatman filter paper No. 41 (2^nd filtration) and absorbance was taken at 205 nm. % variation was compared for standard solution after 1^st filtration and 2^nd filtration. There was negligible changed in absorbance was obtained as shown in Table 2.

Table 2. Filter paper validation

Sr. No.	Standard solution	Absorbance	% Variation for Whatman filter paper No. 41
1.	Without filtration	0.4672	_
2.	Filtered through Whatman filter paper No. 41 (1st filtration)	0.4721	1.040
3	Filtered through same Whatman filter paper No. 41 (2nd filtration)	0.4593	1.720

 

 

2.8. Assay:

The assay of drug in coated pellet was calculated for all the sustained-release pellet formulations. The study was carried out in triplicate. Results of assay are tabulated in Table 3. The assay values were found satisfactory, which ensures dosage uniformity and meets requirements of U.S.P.

 

Table 3

Drug	Labeled Claim, mg	Amount found (n=3)	% Assay	Average mean (%)
Phenylpropanolamine hydrochloride	50	49.1 49.5 48.6	98.2 99.1 97.2	98.1

 

USP limit: Phenylpropanolamine Hydrochloride Extended-Release Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of phenylpropanolamine hydrochloride (C₉H₁₃NO·HCl).⁷

 

2.9. Validation of the Method:

ICH guidelines were followed for the validation of the analytical procedure. The method was validated for precision, repeatability and accuracy.⁸ Instrumental precision was checked by repeated scanning of the PPH. The repeatability of the method was affirmed by analyzing 10ppm. Variability of the method was studied by analyzing aliquots of standard solution of PPH on the same day (intra-day precision) and on different days (inter-day precision).

 

RESULTS AND DISCUSSION:

The UV-Visible spectrometry method was optimized with a view to develop analytical method for phenylpropanolamine hydrochloride (PPH) in PPH sustained release pellets. Absorbance of pure drug solution was taken by using UV-Visible spectrophotometer. From UV-Spectrum, the UV-operating conditions were selected. Calibration curve was found to be linear. The correlation of coefficient (r²) obtained was found to be 0.998 for phenylpropanolamine hydrochloride. It was observed that the concentration range showed a good relationship. Filter paper validation was done by filtering standard solution through Whatman filter paper No. 41 (1st filtration and 2nd filtration) and absorbance was taken at 205 nm. There was negligible changed in absorbance was obtained. The % assay or average amount of phenylpropanolamine hydrochloride found to be 98.1% in each capsule.

 

CONCLUSION:

The analytical method for phenylpropanolamine hydrochloride (PPH) in PPH sustained release pellets was found to be accurate and precise as per the ICH Guidelines. Thus, the proposed UV-Visible Spectrophotometry method can be successfully applied for the routine quality control analysis of phenylpropanolamine hydrochloride from their fixed dosage form. The drug is water soluble so that this method is economical.

 

ACKNOWLEDGMENTS:

The authors acknowledge Themis Laboratories Pvt. Ltd., Thane (presently known as Inventia Healthcare Pvt. Ltd., Thane), for providing all the materials and facilities required for research work.

 

REFERENCES:

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4.       Andersson KE and Bende M. Adrenoceptors in the control of human nasal mucosal blood flow. Ann Otol Rhinol Laryngol. 1984; 93: 179-182.

5.       Johnson DA and Hricik JG. The pharmacology of α-adrenergic decongestants. Pharmacotherapy. 1993; 13: 110S-115S.

6.       Hoffman BB and Lefkowitz RJ. Catecholamines and sympathomimetic drugs. In Goodman and Gilman's. The pharmacological basis of therapeutics, Edited by Hardman JG and Limbird LE. McGraw-Hill, New York, Pergamon Press. 1990; pp. 187-220.

7.       United States Pharmacopoeia 27-NF-22: Asian edition, USP Convention Inc., 1476 (2004).

8.       International Conference on Harmonization (ICH) Hormonised Tripartite Guidelines, Text on validation of analytical procedures Q2A, adapted 27 Oct 1994.

 

 

Received on 15.01.2010        Modified on 11.03.2010

Accepted on 13.04.2010        © AJRC All right reserved