Bioanalytical technique: a quality check for pharmaceutical dosage forms

Quality, safety and efficacy these are the endeavours required to be addressed meticulously for any drug development process. World regulatory agencies are repeatedly and continuously reminding the pharmaceutical manufacturer to abide by these three major requirements for any dosage form preparation either new drug entity or imitated generic drug. Bioavailability of drugs at target sights considered as a major indicator of the quality and efficacy of any therapeutic agent. Bioavailability of drug is often evaluated by bioequivalence (BE) of the drug with the reference drugs or already tested drugs. Bioanalysis of drug substances plays a critical role to determine the effectiveness of the bioequivalence results. In Malaysia, the regulatory agency responsible for overseeing the approval of drugs and ensuring their quality, safety, and efficacy is the National Pharmaceutical Regulatory Agency (NPRA). Bioequivalence result is important for the evaluation of generic drugs and NPRA follows the guidelines set by the World Health Organization (WHO) for determining bioequivalence. Thus, bioanalytical techniques become the key quality checking tool for the determination of the quality and efficacy of any drug dosage forms. At IIUM, we strive towards the excellence of quality manufacturing of drug dosage forms through its PICS GMP compliant manufacturing plant IKOP Sdn Bhd. NPRA requires that generic drugs demonstrate bioequivalence to their reference listed drug before they can be approved for sale and use in Malaysia. To comply with the NPRA requirement we have developed several bioanalytical assay for different classes of drugs such as antihypertensive, antidiabetic, NSAID, antihistamin etc. Different HPLC and LCMS technique was adopted to develop and validate bioanalytical technique for the determination of drugs in human plasma or serum. Design of experiment was used to optimise the extraction technique for a better sample preparation. USFDA, EMA, ICH and ASEAN BE guideline was followed for the development and validation of the bioanalytical techniques

Awareness of herbal products among students at local university in Malaysia

Purpose: Herbal medicines are the most common type of traditional and complementary medicines (T & CM). T & CM have been used to diagnose and prevent diseases, restore the body’s function, and maintain or improve health. Malaysia has different ethnic groups with different beliefs and cultures. For the three dominant races, Malay, Chinese and Indian, traditional and herbal medicines are a long-standing practice. Hence, there is a common perception that the use of herbal products is better than the commercially available pharmaceutical drugs, which are deemed to contain harmful chemicals and have adverse side effects. This study aims to determine consumer’s usage of herbal products and the respondent’s perception of these product’s safety and efficacy. Method: A cross-sectional survey was performed using a self-administered questionnaire on a sample of 377 from different ethnic groups. Chi-square, Mann Whitney, Kruskal Wallis and Spearman correlation were applied for data analysis. Result: This study found significant differences in perception among the respondents from different ethnic backgrounds. Of 300 herbal product (np) users, Chinese (n=210) respondents are likely to consume natural products compare to Malay (n=54), ‘Others’ (n=34) and Indian (n=32). Malay respondents have a higher perception towards the safety of the products while Chinese respondents that herbal products might have lower nutritional value. Lastly, Indian respondents perceive that it is safer to consume natural products after consulting physicians and disagree that herbal products are more effective than conventional medicines. Conclusion: This study’s findings could help policymakers and health service providers to understand the pattern of herbal product consumption among Malaysians

METHODOLOGY FOR THE ALTERATION OF HAZARDOUS SOLVENTS IN DRUG SYNTHESIS

Hazardous solvents have a high potential for causing acute health risks, including serious health problems such as cancer. They should be avoided or limited in pharmaceutical and chemical synthesis owing to the health hazards and safety issues. A method of amide coupling reaction was developed employing the recommended solvents to replace the hazardous solvents. The reactions were observed using the RP-HPLC method to detect reaction rate of aniline and benzoic acid to produce N-phenyl benzamide. 68.33%, 79.25% and 89.81% yields were synthesized using the solvents: acetone (Ace), dimethyl sulfoxide (DMSO), and ethanol (EtOH) respectively while 87.60% was produced by hazardous solvent: N, N-dimethyl formamide (DMF). Using this approach, adjusting the pH10 of the organic solvent increases reaction yield up to 34.67%, 4.65%, and 3.84% for Ace, DMSO, and EtOH, respectively. In drug synthesis, the proposed method can be applied in wide range to get the protection from the risks of hazardous solvents. The method can be anticipated in future to be an exciting basic method in synthetic chemistry

Effectiveness of Peat Coagulant for the Removal of Textile Dyes from Aqueous Solution and Textile Wastewater

Tropical peat soil after chemical modifica tion was found to be an effective coagulant for clarification of some textile dyes from their aqueous solution. A thorough comparative study with conve ntional coagulant had also been done. Results show that it can remove reactive, vat and disperse dyes from their 50 mgIL aqueous solution. It was found that the removal for reactive blue 19 and cibacron brilliant red was 99% and 97%, vat blue 14 and disperse red 72, 98% and 97% respectively. Even though our study with 10% alum and PAC (Poly Aluminium Chloride) solution showed a 100% removal of disperse and vat dyes, both of them showed a poor removal of two reactive dyes. Peat coagulant had a wide pH working range, however its optimum pH range was from pH 3 to 5. On the other hand, alum and PAC showed specific working pH of 5 for two reactive dyes, but they showed wide pH working range for disperse and vat dyes. The mechanism for coagulation by peat coagulant was proven as charge adsorption neutralisation process. The study with textile wastewater shows a 94% removal of colour and 98% removal of suspended solids by using peat coagulant

Effect of Mahkota Dewa fruit extract on kidney functions in mice

Mahkota dewa fruit is known for its antidiabetic effect and is commonly used in Malaysia, Indonesia, Philippine, Thailand and Oceania. However, there is still insufficient information available to validate the safe dose of the fruit extract for human use. Hence, the aim of this research was to determine the safe dose for renal function in mice. Materials and Methods: [MM2] The subcritical liquid carbon dioxide extract of Mahkota dewa fruit was prepared and administered via oral gavage to two groups (normal and 3000 mg/kg bw based on up and down procedure) for acute toxicity according to the OECD-425, 2008 and five groups viz. normal control, 250, 500, 1000 and 2000 mg/kg bw for sub-acute toxicity according to the OECD-407, 2008. The renal function parameters such as urea, creatinine and morphological observation of kidney tissue were analysed. Results: [MM3] The extract exhibited no mortality, morbidity, and no change in general behaviour up to a dosage of 3000 mg/kg body weight (LD 50 >3000 mg/kg). [MM4] The result of urea markedly rose to 76.71 mg/dL and 87.38 mg/dL compared to the control group (48.46 mg/dL) at doses of 1000 and 2000 mg/kg bw respectively. Similarly, creatinine value was also increased 0.87 mg/dL and 0.94 mg/dL compared to the control group (0.61 mg/dL) at doses of 1000 and 2000 mg/kg bw respectively. Moreover, the abnormal morphological finding was also found such as dilated tubules, focal degeneration, apoptosis, renal lesions/tissue haemorrhages of kidney tissue in the same doses (1000 and 2000 mg/kg bw. On the other hand, normal biochemical and histological findings were found at doses of 250 and 500 mg/kg bw in comparison to the normal control group. Conclusion: The findings revealed that Mahkota dewa fruit extract up to 500 mg/kg bw is a safe dose that would offer a greater therapeutic benefit without causing any nephrotoxicity effects. However, further clinical trials are still warranted to determine a safe dose before its commercialization

In vitro α-glucosidase inhibitory activity of Mahkota Dewa fruit flesh using different extraction methods

Purpose: Before using any plant for medicinal purposes, the proper extraction method must be considered for the bioactive compounds, which can be either polar or non-polar or both, and its advantages and disadvantages, depending on the selection process. The aim of this research was to compare the α-glucosidase inhibitory activity of Mahkota dewa fruit flesh using conventional and non-conventional extraction techniques. Method: The extraction was performed by heat reflex (HR), supercritical fluid extraction (SFE), and subcritical carbon dioxide (Sub-CO2) extraction using different temperatures, pressure, solvent ratio, flow rate. The optimized extracts were analyzed for a-glucosidase inhibitory activity with Saccharomyces cerevisiae enzyme. Result: The yields and α-glucosidase inhibitory activity of the Mahkota dewa extracts were analyzed. The yield was obtained in the order of HR>SubCO2>SFE on the other hand the IC50 value of α- glucosidase inhibitory activity was estimated in the order of SubCO2> HR >SFE due to its mild operating temperature and relatively low-pressure condition. Because carbon dioxide is a non- polar solvent that prefers mostly non-polar compounds, adding a co- solvent increases its polarity and improves the ability to extract more polar compounds. Furthermore, after depressurization, carbon dioxide can be easily separated from the end product. As a result, SubCO2 is the most practical extraction method for achieving higher quality of extract. Conclusion: The composition and bioactivities of extracts of natural products were typically influenced by the extracting method, solvent, and temperature

Assessment of liver acute toxicity in mice of the God’s crown extract

God’s crown (GC) is a traditional herbal plant that grows all year long. It is widely available throughout the Southeast Asian region, with the highest concentrations in Malaysia, Indonesia, and Oceania. In traditional and complementary medicine various parts of GC have been used effectively in preventing and controlling symptoms of different diseases such as kidney, diabetes, stroke, haemorrhoids, cancer, migraine, impotence, allergies, heart disease, acne, and other skin problems. The use of herbal products in a safe manner is extremely important for human beings. But there are still insufficient data on GC acute toxicity and safety. As a result, toxicological testing of GC extracts in experimental animals is a requirement for clinical trials and future therapeutic applications. The aim of this research was to analyze the acute toxicity in the mice model of GC extract. The subcritical extract of GC was designed and administrated in mice for the evaluation of acute toxicity and hepatoprotective activity according to the OECD guidelines 425. The liver function parameters such as alkaline phosphatase (ALP), aspartate aminotransferase (AST), total protein (TP), alanine aminotransferase (ALT), and morphological observation of liver tissue were analyzed consequently. The subcritical extract did not show any mortality and no changes in general behavior up to a dose of 3000 mg/kg body weight (3000mg/kg>LD 50 ). The histopathological profile of the extract-treated liver tissue demonstrated similar morphology as that of normal controls at doses 500 mg/kg body weight. On the other hand, acute toxicity is reflected by the various investigated parameters apart from mild liver histopathological inflammatory changes which reflect mild liver injury induced by the 1000mg/kg body weight. As a result, when developing GC-based phytomedicine, it is important to consider the selection of an appropriate dose that will provide better activity while minimizing adverse side effects

A review on the development of granulation technology in the past two decades

Granulation is a technique that convert fine powder particles to granules which form appropriate agglomerate. It’s main function is to improve the powders flow and compressibility properties as well as to prevent segregation of the blend components. Traditionally, there are three types of granulation methods namely dry granulation, wet granulation and direct compressing. But, each one of these traditional methods has different disadvantage which prompted the researchers to modify and find new technique to granulate the powder. Among the new granulation technique are steam granulation, melt granulation, moisture activated dry granulation, foam granulation, pneumatic dry granulation technology and thermal adhesion granulation. Choosing a technique depends on the knowledge of advantages and disadvantages of each technique and how appropriate it is to the characteristics of each ingredient. This review mainly focusses on new techniques in granulation technologies for granules production

Co-processed excipients: a revisit of its development in the past two decades; a review

A pharmaceutical excipient is a substance acts as a carrier incorporates active pharmaceutical ingredients. Excipient selection focuses on desirable characteristics of excipients. Limitations of using excipients which affect the characteristics of the granules and tablets. Co-processed excipients are produced by integrating one excipient into the other excipient at particle level. Such combination of two or more pharmacopeial or non-pharmacopeial excipients does not involve chemical reaction and only involve physical properties changes which is not possible by simple physical mixing. The introduced multicomponent-based excipients for formulation to obtain better features and tableting properties. The objectives of this revisit to discuss the development of co-processed excipients in the past two decades. This review summarizes the advantages of co-processed excipient, the manufacturing process, compilation of co-processed excipients in the literature, limitations, evaluation methods and future development of co-processed excipient. Co-processed excipients will undoubtedly attract attention from academia and pharmaceutical industry as more newer combinations of excipients and newer ways of co-processing become available Besides, rather using numerous excipients in formulation, it allows for the development and usage of single multifunctional excipients

The effect of selected commercially available mouth-rinses vs. curcumin photosensitizers in an artificial mouth model mimicking their use before meals on early colonizers single species biofilm

Abstract. – OBJECTIVE: The aim of the study was to determine the bacterial-adherence to the experimental pellicle pretreated with commer- cially available oral-rinse/photosensitizer (mim- icking use of oral-rinse/photosensitizer beforemeals). MATERIALS AND METHODS: An artificial mouth (NAM) system was used for the devel- opment of single-species biofilm (Actinomyces viscosus, Sreptococcus mitis and Streptococ- cus sanguinis respectively). Two commercially available oral-rinses containing active ingredi- ents [Essential oils (EO) and Chlorhexidine glu-conate (CHX) were used. Curcumin photosensi-tizer (PS) was used as a photosensitizer against the microbes. For the adherence study, the ex-perimental pellicle on the beads (in the capillary tubes of the NAM system) was pretreated with the oral-rinse and photosensitizer before the in-oculation of bacteria; this would resemble the use of rinse/photosensitizer before meal. The bacterial population of the biofilm was determined using serial dilution assay and expressed as colony forming unit per ml. Deionized distilled water was used in place of oral-rinse/ photosensitizer and served as a negative-control. For the qualitative study, bacterial population viewing was carried out using Scanning Electron Microscope (SEM). RESULTS: It was observed that on treatment with the oral-rinses the bacterial population of S.mitis, S.sanguinis and A.viscosus (adherence) was significantly reduced where the reduction was less for EO-based oral-rinse compared with that of CHX and curcumin PS in the following se- quence EO<CHX<PS (p<0.05). CONCLUSIONS: From the results, it appears that curcumin photosensitizer and oral-rinses contain CHX to be preferably used before-meal and EO after-meal