Analysis of low active-pharmaceutical-ingredient signal drugs based on thin layer chromatography and surface-enhanced Raman spectroscopy.

Active pharmaceutical ingredients (API) embedded in the excipients of the formula can usually be unravelled by normal Raman spectroscopy (NRS). However, more and more drugs with low API content and/or low Raman scattering coefficient were insensitive to NRS analysis, which was for the first time defined as Low API-Signal Drugs (LASIDs) in this paper. The NRS spectra of these LASIDs were similar to their dominant excipients' profiles, such as lactose, starch, microcrystalline cellulose (MCC), etc., and were classified into three types as such. 21 out of 100 kinds of drugs were screened as LASIDs and characterized further by Raman microscopic mapping. Accordingly, we proposed a tailored solution to the qualitation and quantitation problem of these LASIDs, using surface-enhanced Raman spectroscopic (SERS) detection on the thin layer chromatographic (TLC) plate both in situ and after-separation. Experimental conditions and parameters including TLC support matrix, SERS substrate, detection mode, similarity threshold, internal standard, etc., were optimized. All LASIDs were satisfactorily identified and the quantitation results agreed well with those of high performance liquid chromatography (HPLC). For some structural analogues of LASIDs, although they presented highly similar SERS spectra and were tough to distinguish even with Raman microscopic mapping, they could be successfully discriminated from each other by coupling SERS (with portable Raman spectrometer) with TLC. These results demonstrated that the proposed solution could be employed to detect the LASIDs with high accuracy and cost-effectiveness.

Risk assessment of supply chain for pharmaceutical excipients with AHP-fuzzy comprehensive evaluation.

As the essential components in formulations, pharmaceutical excipients directly affect the safety, efficacy, and stability of drugs. Recently, safety incidents of pharmaceutical excipients posing seriously threats to the patients highlight the necessity of controlling the potential risks. Hence, it is indispensable for the industry to establish an effective risk assessment system of supply chain. In this study, an AHP-fuzzy comprehensive evaluation model was developed based on the analytic hierarchy process and fuzzy mathematical theory, which quantitatively assessed the risks of supply chain. Taking polysorbate 80 as the example for model analysis, it was concluded that polysorbate 80 for injection use is a high-risk ingredient in the supply chain compared to that for oral use to achieve safety application in clinic, thus measures should be taken to control and minimize those risks.

Pharmacists’ participation in the documentation of medication history in a developing setting: an exploratory assessment with new criteria / Participación de los farmacéuticos en la documentación del historial de medicación en un país en desarrollo: evaluación exploratoria con nuevos criterios

Objective: To assess the impact of pharmacists' participation on the frequency and depth of medication history information documented in a developing setting like Nigeria. Method: The study consisted of two phases. The first phase was a baseline cross-sectional assessment of the frequency and depth of medication history information documented by physicians in case notes of systematic samples of 900 patients that were stratified over 9 Medical outpatients Units at a premier teaching hospital in south western Nigeria. The second phase was an exploratory study involving 10 pharmacists who conducted cross-sectional medication history interview for 324 randomly selected patients. Results: 49.2% of patients, whose medication history were documented at the baseline, by physicians, were males; while 50.3% of patient interviewed by pharmacists were male. Mean age (SD) of males and females whose medication histories were documented by physicians and pharmacists were 43.2 (SD=18.6), 43.1 (SD=17.9) years and 51.5 (SD=17.6), 52.1 (SD=17.4) years respectively. The frequency of medication history information documented by pharmacists was significantly higher for twelve of the thirteen medication history components (P < 0.0001). These include prescription medicines; over the counter medicines; source of medicines; adverse drug reactions; allergy to drugs, allergy to foods, allergy to chemicals; patient adherence; alcohol use; cigarette smoking; dietary restrictions and herbal medicine use. The depth of medication history information acquired and documented by pharmacist was significantly better for all the thirteen medication history components (P<0.0001). Conclusion: Pharmacists' participation resulted in significant increase in frequency and depth of medication history information documented in a developing setting like Nigeria. The new medication history evaluation criteria proved useful in assessing the impact of pharmacists' participation (AU)

Objetivo: Evaluar el impacto de la participación de los farmacéuticos en la frecuencia y profundidad de la información registrada en los historiales de medicación en un país en desarrollo como Nigeria. Métodos: El estudio consistió en dos fases: la primera fase fue una evaluación basal transversal de la frecuencia y profundidad de la información registrada en los historiales de medicación por los médicos como casos de muestras sistemáticas de 900 pacientes que se estratificaron de 9 unidades ambulatorias en un hospital universitario en el suroeste de Nigeria. La segunda fase fue un estudio exploratorio que envolvió a 10 farmacéuticos que realizaron entrevistas transversales de historias de medicación a 324 pacientes aleatoriamente seleccionados. Resultados: El 49,2% de los pacientes, cuyo historial de medicación fue documentado en el inicio por los médicos eran mujeres; mientras que el 50,3% de los entrevistados por los farmacéuticos eran hombres. La media (DE) de edad de los hombres y las mujeres con historiales de medicación registrados por los médicos y farmacéuticos era de 43,2 (DE=18,6), 43,1 (DE=17,9) años y 51,5 (DE=17,6), 52,1 (DE=17,4) años, respectivamente. La frecuencia de información registrada en los historiales de medicación por los farmacéuticos fue significativamente más alta para 12 de los 13 componentes (P<0,0001). Estos incluían los medicamentos prescritos; los medicamentos OTC; la fuentes de medicamentos; las reacciones adversas; la alergia a medicamentos, alimentos o substancias químicas; el cumplimiento del paciente; la ingesta de alcohol; el tabaco; las restricciones dietéticas y el uso de plantas medicinales. La profundidad de la información de los historiales de medicación adquirida y documentada por los farmacéuticos era significativamente mejor para todos los 13 componentes de los historiales (p<0,0001). Conclusión: La participación de los farmacéuticos produjo un incremento significativo en frecuencia y profundidad de la información registrada en los historiales de medicación en un país en desarrollo como Nigeria. Los nuevos criterios de evaluación de historiales de medicación probaron ser útiles para evaluar el impacto de la participación de los farmacéuticos (AU)

[Suggestions for improving quality control of excipients used in processing of crude drugs].

To propose for improving the quality control of excipients used in processing of crude drugs. The quality control and administration of excipients in processing of crude drug were reviewed, and problems existed were analyzed. For enhance the excipients quality control, more effort should be focused on fundamental research, improving of management mechanism and construction of quality control system.

Application of instrumental colour measurement in development and quality control of drugs and pharmaceutical excipients.

This review covers applications of instrumental colour measurement using tristimulus colorimetry in development, stability testing, production and quality control of synthetic and natural drugs, dosage forms and pharmaceutical excipients in the last three decades.

Recent developments in the risk assessment of potentially genotoxic impurities in pharmaceutical drug substances.

Controlling the quality of medicines is just as important as demonstrating efficacy. The International Conference on Harmonisation has published general guidance on the quality and safety assessment of impurities in pharmaceutical drug substances and drug products. More recently, the European Medicines Evaluation Agency has published a guideline focusing on limits for genotoxic impurities. This is based on a Threshold of Toxicological Concern (TTC) derived from animal carcinogenicity data using multiple worst case assumptions to estimate a daily dose (1.5 microg/day) associated with a lifetime cancer risk of 1 in 100,000, a risk level considered acceptable for genotoxic impurities in human medicines. Based on these assumptions, presentation of the TTC as a single figure infers an unwarranted level of precision and supports the adoption of a more flexible approach by regulatory authorities when evaluating new drug products; a range within fivefold of the TTC limit would seem sensible. Furthermore, the limit is based on 70 years continuous daily exposure, a scenario that is uncommon for most medicines and irrelevant to the preregistration clinical development phase. To address this latter point, a staged TTC has been developed that proposes limits based on shorter durations of treatment, e.g., up to 1 year. Based on recent history, this approach has been acceptable to some authorities but not to others, and it is imperative that steps are taken to reach a common agreement between the pharmaceutical industry and regulatory authorities globally in order that new medicines can continue to be developed and delivered to benefit patients in a safe and timely manner.

Preparation and in vitro characterization of self-nanoemulsified drug delivery system (SNEDDS) of all-trans-retinol acetate.

PURPOSE: To prepare a self-nanoemulsified drug delivery system (SNEDDS) of all-trans-retinol acetate, with enhanced dissolution and better chance of oral absorption. METHOD: All-trans-retinol acetate SNEDDS was prepared using different concentrations of soybean oil (solvent) Cremophor EL (surfactant) and Capmul MCM-C8 (co-surfactant). Particle size and turbidity of the SNEDDS were determined after adding water to the oily solution. Dissolution profile of SNEDDS filled in hydroxyl propyl methyl cellulose (HPMC) capsules was determined by using water in USP apparatus 2. Ternary phase diagrams were constructed to identify the self-nanoemulsified region. The SNEDDS were evaluated by the visual observation, turbidity in nephrometric turbidity units (NTU), mean particle size (microm) and Fourier transformed-infrared spectroscopy (FT-IR). SNEDDS were thermally characterized using differential scanning calorimetry (DSC) to ensure the compatibility of the SNEDDS ingredient. RESULTS: From the data obtained in this work, it was clear that surfactant to co-surfactant ratio has the main impact on the physical characteristics of the emulsion formed. The optimum surfactant to co-surfactant ratio was found to be 2:1 (37.5-50% for Cremophor EL, and 18.75-25% for Capmul MCM-C8). With this ratio, the resultant nanoemulsions obtained have a particle size range of 0.103-0.051 microm, turbidity range of 18.12-2.18 NTU and t30 values (cumulative% all-trans-retinol acetate dissolved in 30 min) of 90.42-99.5. Also the thermograms obtained from DSC experiments showed that there is no incompatibility or interaction between the SNEDDS ingredients (soybean oil, Cremophor EL, and Capmul MCM-C8) and all-trans-retinol acetate. CONCLUSION: The present study revealed that the self-nanoemulsified drug delivery system of all-trans-retinol acetate increased its dissolution rate and has the potential to enhance its bioavailability without interaction or incompatibility between the ingredients.

Pharmaceutical excipient development: the need for preclinical guidance.

Pharmaceutical excipients have a vital role in drug formulations, a role that has tended to be neglected as evidenced by the lack of mechanisms to assess excipient safety outside a new drug application process. Currently, it is assumed that an excipient is "approved" when the new drug formulation, of which it is a constituent, receives regulatory acceptance. Existing regulations and guidelines indicate that new (novel) excipients should be treated as new chemical entities with full toxicological evaluation. No guidance is available for potentially useful materials (essentially new excipients) available from other industries, e.g., food additives or for established excipients with a new application, e.g., dose route change. However, despite this situation, drug companies are actively evaluating new materials or applying new uses to established excipients. Recently developed excipients (e.g., materials giving "sugar-free" status to medical preparations, the cyclodextrins, and the hydrofluoroalkane inhalation propellants) and excipients undergoing development (e.g., chitosan, various enteric coating substances, liposomes, polymers derived from glycolic and lactic acids, and vaccine adjuvants) are all discussed. In light of many other areas of drug development having recently benefited from new or updated regulatory guidance, specific guidance to assist companies in the development of their excipients is urgently needed. Also, an excipient testing strategy would be an excellent topic for inclusion for International Conference on Harmonisation (ICH) consideration. Such guidance/discussion would complement the current advances in pharmacopoeial standardization of excipient quality. As a consequence, it may be possible to have excipients reviewed by a committee of an international pharmacopoeia with the safety data assessed by elected experts and published.