Evaluation of Antihypertensive Herbal Products in Raw and Finished Dosage Form: Quantification of Adulterants and Undeclared Allopathic Contents

Abstract

Hypertension is the most common cardiovascular disease around the globe. A variety of chronic diseases including hypertension has been treated using herbal medicines because herbal products are considered non toxic and safe therefore indicated for primary health care. The belief that herbal products are economical and safe, people in developing countries like Pakistan always preferred herbal drug products over synthetic allopathic medicine. The economical cost of these products has increased its use all around the world and they are in high demand now days. The escalating use of these remedies bring concerns for health regulatory agencies, about its misuse and possible toxic effects as people commonly used herbal medicine are often unaware of it. These products may be contaminated with toxic synthetic compounds, chemical toxins, microbes and adulterated with undeclared allopathic drug contents. Manufacturing protocols for production and quality control procedure required for herbal products are often Inadequate; due to which contaminants become additional part of these drug products during manufacturing and improper handling. Therefore; herbal medicines demands a critical analysis of safety issues. In current study different herbal remedies indicted for hypertension were evaluated both in raw material and finished dosage. Evaluation of the procured herbal drug products were carried out using state of the art techniques. Pharmaceutical properties for raw and finished dosage form were evaluated as specified in Pharmacopeias. Heavy metals were identified by AAS (atomic absorption spectrophotometer), Analytical profile index kits (API Kits) were used for identification of microbial contaminant strains and adulterated allopathic ABSTRACT drugs and synthetic steroids were quantified using advanced HPLC analytical techniques. Pharmaceutical parameters required for standard dosage form was found vary both in raw and finished form of the tested drug products. The MC (moisture contents) and (loss on drying) LOD % were observed beyond specified limits. Similarly, variation in weight of Tablets of products (P1, P2, P6, P12, P16, P17, P19, and P20) and hardness of products (P1, P3, P8 and P11) were not in specified limits. Products (P3, P9 and P1) failed the friability test. The concentrations of heavy metal were quantified and found in toxic levels. Product P5 and P9 were found to have toxic concentrations of Iron (1597.20 ppm, 1648 ppm), Lead in Product P5 in concentrations of (61.32ppm, 16.59 ppm), Cadmium in Product P11 and P12 were quantified as (39.53 ppm, 32.31 ppm), Product P15 and P17 were observed to have toxic concentrations of Copper (28.22 ppm, 21.04 ppm), (80.31 ppm,76.27 ppm) of Zinc were quantified in products P16 and P16 and Nickel was found in higher concentrations in Product P9 and P13. Adulterated allopathic drugs including β-blockers, Ca+2 channel blockers, ACE inhibitors and diuretics were identified in different tested herbal remedies and were further quantified according to the manufacturer dose. The allopathic drugs were found in sub-therapeutic and in toxic concentrations. Amlodipine was quantified in Product P12 in highest concentration (20.30 mg/day) while the toxic concentrations of Verapamil (93.50 mg/day) and Nifedipine (38.65 mg/day) were found in Products P2 and P6 respectively. Similarly, Amlodipine and Hydrochlorothiazide combination in the dose range of (10.72 mg/day, 24.75 mg/day) were quantified in Product P5. Moreover adulterations of Atenolol (50.06±1.20 mg/day), Propranolol (28.26±0.06 ii ABSTRACT iii mg/day), Captopril (52.99±0.49 mg/day) and Frusemide (42.02±0.88 mg/day) were observed both in raw and finished form of different herbal products. Synthetic steroidal contents of Prednisolone (4.18±0.02 mg/day, Methyl Prednisolone (13.67±0.50 mg/day), Betamethasone (0.56±0.06 mg/day) and Dexamethasone (1.75±0.11 mg/day) were quantified using standard analytical protocols. This study gives an idea about the potential toxicity caused by herbal products as the public is unaware of its inadequate manufacturing and quality control processes. Moreover adulteration of synthetic compounds without preclinical studies by quacks in order to enhance the efficacy of herbal drug products brings serious concerns to public health and their administration may cause severe toxicity. Therefore to maximize consumer safety, appropriate rules and regulations must be developed for the registration, production and marketing of herbal remedies.