Herbal Drug Development from Traditional Formulations: Refocusing Pharmaceutics and Posology for Accelerated Validation.

Background: The World Health Organization (WHO) recommended that the toxicity data of a traditional medicine (TM) product that has been in use for 20 years or more without untoward effects should be determined, as the first step in its research and development (R&D). Such data in conjunction with efficacy data would be used to develop an appropriate dosage form of the product. A key objective in researching such a product is to validate the basis of the therapy, including the formula. Such validation, and any attempt to modernize the product, should be guided by an understanding of the traditional know-how. The Nigerian National Institute for Pharmaceutical Research and Development (NIPRD) utilized this approach in developing Niprisan, an antisickling drug, based on a TM product used since antiquity in Yoruba Medicine. Aim: This article aimed to advocate the continuance and improvement of the WHO model of herbal drug research and regulation (HDRR) as the most logical approach for adoption by researchers and regulators. Methodology: NIPRD’s adoption of the WHO model since 1989 was reviewed in parallel with trends in herbal drug research worldwide; and within the contexts of regulatory practices by Nigeria’s National Agency for Food and Drug Administration and Control (NAFDAC) and the European Medicines Evaluation Agency (EMEA), with a view to identifying more effective strategies within the WHO paradigm for HDRR. Conclusion: Drug regulatory agencies (DRAs) like NAFDAC require effective laws, policies and quality management systems (QMS) to execute their mandates effectively. On the other hand, NIPRD’s output depends upon proper actions by a seasoned and responsive DRA. Therefore, noting that NIPRD and NAFDAC were both created by military decrees in 1989 and 1992 respectively, rather than by parliament acts, it is recommended that in addition to instituting more effective laws and policies to regulate NAFDAC, both NIPRD and NAFDAC need to adopt and implement suitable QMS for self-regulation, eg: ISO 9001 for whole organizations; and ISO/IEC 17250 for the laboratories.

Standardization of Andrographis paniculata, Mitracarpus scaber and Nauclea latifolia Herbal Preparations as per European and Nigerian Drug Regulations.

Background: Herbal drug standardization (HDS) is multidisciplinary with botany and chemistry working together to facilitate decisions on production of herbal medicines. The common reasons for HDS are: i) it creates the need for establishing botanical identity; ii) it is necessary for establishing dosage and iii) it facilitates industrial production and good manufacturing practice (GMP). Aims: To outline the strategies being used to standardize Conavir, Niprd-AM1 and Niprifan and to show that HDS is the ideal strategy for herbal drug development (HDD) from traditional medicines (TMs). Methodology: Relevant data on: i) the regulatory requirements of Europe’s Medicines Evaluation Agency (EMEA) and Nigeria’s National Agency for Food and Drug Administration and Control (NAFDAC) and ii) on Andrographis paniculata (AP), Mitracarpus scaber (MS) and Nauclea latifolia (NL) were reviewed. Crude herbal drugs (CHDs) from aerial parts each of AP and MS and from roots of NL and the active crude extracts (ACEs) derived from them were studied using standard botanical, phytochemical and physicochemical techniques with the aim of standardizing them for production. The ACEs from AP (Conavir) and from NL (Niprd-AM1) were dry water extracts. The ACE from MS (Niprifan) was a dry ethylacetate extract. Results: The regulatory provisions of NAFDAC for herbal preparations were broadly similar to those of EMEA but the latter proved more explicit in many respects. Furthermore, the results on the CHDs and ACEs adequately meet the requirements of the two agencies. Conclusions: The results here provided and those reported elsewhere collectively furnish the data needed for drawing-up the registration dossiers of AP/Conavir, NL/Niprd- AM1 and MS/Niprifan as per EMEA and NAFDAC requirements. But for purposes of further work, it is needful for the GC-MS studies to be amplified and combined with others, so as to facilitate identification of suitable markers and pave the way for studies requiring bioassays.

Phytochemical screening and anticonvulsant studies of ethyl acetate fraction of Globimetula braunii on laboratory animals

Objective: To investigate the phytochemical properties and the anticonvulsant potential of the ethyl acetate soluble fraction of ethanol leaf extract of Globimetula braunii, a plant used in ethnomedicine for the treatment of epilepsy. Methods:The phytochemical screening was carried out using standard protocol while the anticonvulsant activity was studied using maximal electroshock test in chicks, pentylenetetrazole and 4-aminopyridine-induced seizures in mice. Results: The preliminary phytochemical screening carried out on the crude ethanol extract revealed the presence of saponins, carbohydrates, flavonoids, tannins, anthraquinones and steroids. Similarly, tannins, flavonoids and steroids/terpenes were found to be present in the ethyl acetate fraction. In the pharmacological screening, 150 mg/kg of the fraction protected 83.33% of animals against pentylenetetrazole-induced seizure in mice whereas sodium valproate a standard anti-epileptic drug offered 100% protection. In the 4-aminopyridine-induced seizure model, the fraction produced a significant (P Conclusions:These results suggest that the ethyl acetate fraction of Globimetula braunii leaves extract possesses psychoactive compound that may be useful in the management of petit mal epilepsy and lend credence to the ethnomedical use of the plant in the management of epilepsy.

Phytochemical, Physicochemical and Chromatographic Profiling in Quality Control Systems for Select Herbal Medicines (Conavir and Niprd-AM1).

Background: Conavir, an immunostimulant from aerial parts of Andrographis paniculata (AP) and Niprd-AM1, an antimalarial from roots of Nauclea latifolia (NL), are dry water extracts for capsulation. AP and NL have been in use in Asia and Africa for centuries. Purpose: The study aimed to ascertain the criteria for quality assured production of Conavir and Niprd-AM1. Experimental Details: Procedures of World Health Organization (WHO) were applied to evaluate quality parameters of AP/ Conavir and NL/ Niprd-AM1. Results and Discussion: Conavir is granular, greenish brown, intensely bitter and practically odourless. Tests on AP and Conavir revealed alkaloids, saponins, tannins and terpenoids, but cardiac and cyanogenic glycosides (considered toxic) were not detected. Normal phase TLC of AP and Conavir yielded 5 principal spots each, while the reverse phase TLC yielded 6. HPLC fingerprints of AP, Conavir and a reference standard were reproducible but differed from each other. The GC-MS data of Conavir were consistent with the phytochemical profile of AP. Effect of storage suggested that both AP and Conavir were stable for up to 21 months or more. Niprd-AM1 is granular, yellowish brown and faintly aromatic, with an exciting bitter taste. Both NL and Niprd-AM1 contained alkaloids, saponins, flavonoids and terpenoids, but cardiac and cyanogenic glycosides were not detected. Normal phase TLC of NL yielded 9 principal spots, while Niprd-AM1 yielded 5, but the reverse phase TLC yielded 9 for each. HPLC fingerprints of NL, Niprd- AM1 and a reference standard were reproducible but differed from each other. The GCMS data of Niprd-AM1 were consistent with the phytochemical profile of NL. Most of the quality variables of NL and Niprd-AM1 remained unchanged up to the 39th month of storage. Conclusion: The results are consistent with NIPRD’s intention to file for the registration of Conavir and Niprd-AM1 for use in Nigeria.