Propranolol powder was purchased from AKScientific, California. Seven brands of propranolol tablets were purchased from retail pharmacy shops in Okada town of Edo State, Nigeria. The samples were properly checked for their National Agency for Food and Drug Administration and Control (NAFDAC) registration numbers, batch numbers, production, and expiry dates. They were randomly designated as PN-1, PN-2, PN-3 up till PN-7. All other chemicals were of analytical grade and include sodium hydroxide, anhydrous sodium sulfate, methanol, ether.

Instruments used in the study were weighing balance (Mettler Toledo), Hardness Tester (Mosanto, UK), Friability test apparatus (Campbell FTA-20 Single drum), Disintegration Test Apparatus (Esico International, India), M530 FTIR Spectrophotometer (Buck Scientific), and UV-visible spectrophotometer (Cecil CE 2000 series).

Twenty tablets from each of the brands were weighed individually with an analytical weighing balance. The average weights for each brand as well as the percentage deviation from the mean value were obtained.

The identification tests used for propranolol tablets in this study are indicated in the British Pharmacopoeia (BP) 2017 as found below:

Ten tablets of each brand were selected at random and powdered. The quantity of powdered tablet containing 0.1 g propranolol was suspended in 20 mL of water and filtered; the filtrate was made alkaline with 1 M sodium hydroxide, extracted three times each with 10 ml of ether. The combined extract was washed with water until it is free from alkali and dried with anhydrous sodium sulphate. It was then filtered and evaporated to dryness. The residue was dried at 50^ᵒC for 1 hour and the infrared spectrum of each sample was determined. The melting point of the dried residue was also determined as required by the BP. 17

FTIR spectra were obtained by using an FTIR spectrometer. The samples were mixed thoroughly with potassium bromide (KBr) in a Sample to KBr ratio of about 1:5 respectively. The KBr discs were prepared by compressing the powders at a pressure of 5 tons for 5 min in a hydraulic press. Scans were obtained at a resolution of 4 cm−¹,from 4,000 to 300 cm−¹.

The crushing strength was determined with a tablet hardness tester. Five tablets were randomly selected from each brand and the pressure at which each tablet was crushed was recorded.

Twenty tablets from each of the brands were weighed and placed in the friabilator and then operated at 25 rpm for 4 min. The tablets were then de dusted and weighed. The difference in the two weights was used to calculate friability by using the following formula¹⁸:

where Iw is the total initial weight of the tablets and Fwis the total final weight of the tablets

Six tablets of each brand were used for the test in distilled water at 37 °C with disintegration test apparatus employing plastic discs. The disintegration time was taken as the time when no particles remained in the basket of the tester.

A stock solution (100 mL) of 5000 μg/mL was prepared by dissolving 0.5 g of propranolol in phosphate buffer, pH 6.8, and made up to the marked volume with the same solvent. Then 10 mL from this was diluted with phosphate buffer at pH 6.8 and finally, the volume was adjusted up to 100 mL with the same solvent. The resulting solution is called the stock solution of 500μg/mL. The stock solution was then diluted to the desired strength by phosphate buffer pH 6.8.

Serial diluted solutions of 10, 20, 30, 40, 50, 60,70,80, 90, 100 μg/mL of propranolol were prepared from the stock solution (500 μg/mL) with phosphate bufferpH 6.8. The absorbances were taken at 290 nm using a UV-Visible spectrophotometer. A plot of absorbance versus concentration of propranolol was made from which the regression equation was calculated.

The chemical assay test for each brand of propranolol was carried out as stated in the BP 17. The quantity of powdered tablets containing 20 mg propranolol hydrochloride was shaken with 20 mL of water for 10 minutes. Fifty mL of methanol was added and the mixture was shaken for another 10 minutes, sufficient methanol was then added to make 100 mL and it was filtered. Samples were suitably diluted and analyzed by UV spectrophotometry at a wavelength of 290 nm. Determination of propranolol hydrochloride was carried out in triplicate for each brand of tablet using the calibration curve conducted with the standard propranolol.

The dissolution rate test was carried out using the USP apparatus 1 (basket method) in 6 replicates of each brand. The dissolution medium was 900 mL of phosphate buffer at pH 6.8 which was maintained at 37.0±0.5°C. In all the experiments, 5 ml of dissolution sample was withdrawn at 0, 10, 15, 30, 45, and 60 min and replaced with equal volume to maintain sink condition. Samples were filtered and assayed by UV-VIS spectrophotometer at 290 nm. The concentration of each sample was determined from a calibration curve obtained from standard samples of propranolol. The percent dissolutions were computed.

Similarity factor (f₂) has been adopted by the United States Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products to compare dissolution profiles. 18, 19 The dissolution profiles were analyzed by a mathematical model, similarity factor (f₂). Mean dissolution values were employed to estimate the similarity factor (f₂). A factor value of 50 or greater (50-100) ensures the sameness or equivalence of the two products. The equation below was used to calculate similarity factor (f₂):

f2 = 50 •log 1 + 1n∑t=1nRt-Tt2 -0.5•100 

_t is the dissolution value of the reference product at a time 't', and T_t is the dissolution value for the test product at a time.

Each product was found to have been properly strip packed and labeled with the names of the active ingredient, strength, and expiry date. The packets containing the strip packs also had the product name, strength, pack size, batch number, NAFDAC registration, expiry date, and Manufacturer’s name and address boldly written. As shown in Table 1 Table 1, all propranolol tablets collected and investigated were within their shelf lives.

Weight variation or uniformity of the propranolol tablets are shown in Table 2. It was observed that all tablet brands had a coefficient of variance values of < 5 % except PN-6 with a percentage deviation of 7.6%. Thus, tablets from all the samples tested apart from PN-6 can bead judged to have passed the uniformity of weight test for uncoated tablets as stipulated by the British Pharmacopoeia. 17

The melting point of the residue obtained after samples of each brand of the powdered tablet was suspended in water, made alkaline with NaOH, extracted with ether, and filtered was determined. The result obtained is stated in Table 2. The BP 17 states that the melting point for the residue of propranolol should be about 94^ᵒC.

Furthermore, the infrared spectra of the residue of each brand were obtained and spectra are presented in Fig. 2-8. Some functional groups present in propranolol, confirmed by their IR absorption frequency ranges, intensity, and the frequency are presented in Table 3. The spectra of each sample tallies with normal frequency ranges.

The friabilitytest results for the sample brands are shown in Table 2. All the sample brands except PN-5 (with 1.52 % friability) gave a percentage friability of less than 1 % and thus passed the friability test.

Hardness test determined for the brands of tablet range from 1.03±0.17Kg/cm² (PN-6) to 10.70±0.9Kg/cm²(PN-7) as reported in Table 2. Hence the tablets of all brands except PN-5 and PN-6 were satisfactory for hardness based on the BP specification of 4-10 Kg/cm².

Figure 5

Figure 6

Figure 7

Figure 8

All the brands complied with the compendial specifications for disintegration. The BP specification is that uncoated tablets should disintegrate within 15 min and film coated in 30 min while USP specifies that uncoated and film coated tablets should disintegrate within 30 min. All the brands were uncoated tablets while brands PN-1 and PN-2 were film coated. The disintegration time details are as stated in Table 2.

The results showing the content of active pharmaceutical ingredients using UV spectrophotometric method are shown in Table 2. All the tablet batches complied with the British Pharmacopoeia set the limit for propranolol hydrochloride tablet which states that such tablets should contain not less than 92.5 % or more than 107.5 % of the label claim 17. However, PN-6 with a percentage content of 90.07±1.15% did not pass the assay test.

The USP 20 and BP 17 specify that the amount of drug released should not be less than 80% of the labeled amount at 30 min. Findings of this study are presented in Table 4.

All seven brands complied with the USP and BP as shown in Figure 9 and the release profile is almost super imposable. Thus, all the batches passed the dissolution test and their active pharmaceutical ingredient would be readily bioavailable for absorption when ingested. The table showed the percentage of drug dissolved from each brand of the sample drug.

Figure 9

Two dissolution profiles are considered similar and bioequivalent, if f2 is between 50 and 10019. A T90% of 30 minutes is satisfactory and is an excellent goal 21. In this study, parameters like T50%, T75%, T90% and f2 were derived from the dissolution profiles of the different brands. Table 5 showed the f2 values of different brands in respect of brand PN-1.