Pharmaceutical Unit Research Articles

Farmácia Popular Program: pharmaceutical market analysis of antihypertensive acting on the renin-angiotensin system medicines.

This paper aims to analyse changes in the retail pharmaceutical market following policy changes in the Farmácia Popular Program (FP), a medicines subsidy program in Brazil. The retrospective longitudinal analyses focus on therapeutic class of agents acting on the renin-angiotensin system. Data obtained from QuintilesIMS (formerly IMS Health) included private retail pharmacy sales volume (pharmaceutical units) and sales values from 2002 to 2013. Analyses evaluated changes in market share following key FP policy changes. The therapeutic class was selected due to its relevance to hypertension treatment. Market share was analysed by therapeutic sub-classes and by individual company. Losartan as a single product accounted for the highest market share among angiotensin II antagonists. National companies had higher sales volume during the study period, while multinational companies had higher sales value. Changes in pharmaceutical market share coincided with the inclusion of specific products in the list of medicines covered by FP and with increases in or exemption from patient copayment.

Pengaruh Keberadaan Apoteker terhadap Mutu Pelayanan Kefarmasian di Puskesmas Wilayah Kabupaten Banyumas

Due to complexity enhancement of health care services, pharmacists are required to provide their orientation to the patient.The objective of the study are to evaluate the pharmaceutical standard prosedures and measuring the effect of the pharmacist’s presence on the pharmacy services quality in the Community Health Centers (CHCs) of Banyumas districts. The study is an observational analytic categorical through cross sectional approach with colleting data technique is divided into two periods, through observation and structured interviews to the person in charge of pharmaceutical care unit. Based on the analysis, from 38 CHCs it’s found out that 24 (63,16%) CHCs have the pharmac eutical standard procedures and 14 (36,84%) CHC s doesn ’ t have it. However, of the 39 CHC s, there are 33 (84,61 ) CHC s that have pharmacist, 2 (6,06%) CHCs were categorized in a moderate quality and 31 (93,94%) of them categorized as having less quality. While the six (15,38% ) CHC s that d oesn’ t have a qualified pharmacist categorized as having less quality. There ar e the presence of pharmacists towards the availability of the pharmaceutical standard prosedures , have p value of 0.363 (p>0.05) an d the pharma ceutical services checklist with p value of 1.00 ( p >0.05)a t CHCs of Banyumas districts. Conclusionis pharmac eutical services in Banyumas district are n’ t running optimally because presence of pharmacists hasn’t improve the quality.

Evaluasi Kebijakan Perencanaan Obat Instalasi Farmasi Dinas Kesehatan Kota Semarang

Based on the Management of Public Drug and Health Supply Profile, the availability rate of drugs in Pharmaceutical Unit Health Department Semarang 2013-2015 was 107%, 110%, and 109% .The availability rate of drugs in Pharmaceutical Unit Health Department Semarang for 3 years in a row exceeds 100% showed a weakness in drugs planning process. Objective of this study was to analyse the planning process of drugs. This was descriptive research with qualitative method. Research subject is the primary respondents who developed drug planning policy and triangulation respondents who implement the drugs planning policy. Research object was Pharmaceutical Unit Health Department Semarang and Puskesmas. Data collected by observation, documentation study and depth interview and analysed using content analysis. The result showed that drugs selection was according to FORNAS and DOEN stated by Ministry of Health. The compilation stage of drugs application using data according to LPLPO and LB-1. The calculation of drugs necessity used combination method between consumption method used by clinic and epidemiology method for program medicine. Based on the consumption method formula, the current leadtime in Pharmaceutical Unit Health Department Semarang was too high (6 months) which caused the supplies more than 100 %. The drugs necessity projection budget already sufficient because it was supported from several sources, such as APBD2, APBD1, APBN, DAK, JKN. The adjustment of drugs supply planning used VEN Analysis. It is suggested that Pharmaceutical Unit Health Department Semarang should shortened the current leadtime and increase the socialization of drugs guidelines therefore Puskesmas able to implement the epidemiology method

The Pharmaceutical Drying Unit Operation: An Industry Perspective on Advancing the Science and Development Approach for Scale-Up and Technology Transfer

The drying unit operation is used extensively in the pharmaceutical industry, but often a lack of understanding of the impact of the drying process parameters on active pharmaceutical ingredient critical quality attributes can create challenges during development. A working group within the Enabling Technologies Consortium identified common challenges in pharmaceutical drying development, including material constraints for scale-up studies and transferring to different equipment types and sizes. This manuscript surveys current practices within the industry for drying development related to chemical and physical stability, drying kinetics, and powder properties and highlights common development gaps for improving drying development workflows within the industry. The ultimate goal is to encourage further fundamental research and technological advancements for improving the drying development workflow.

Centrally Prepared Cytotoxic Drugs: What Is the Purpose of Their Quality Control?

AbstractTo assess the quality of centrally prepared cytotoxics a global approach is being implemented by pharmacists. A risk analysis is performed, and then many in-process controls are proposed. The aseptic process and the material are also fully validated. Moreover the skills of pharmacy technicians are being checked and monitored over time. This short opinion paper discusses the place of in-process quality control within the quality system applied to cytotoxic preparations. It also discusses the pros and cons of analytical control of the final product versus continuous control of each preparation step by eye witness or an electronic device such as a camcorder. Finally the relevancy of controls is discussed in function of different cases and of the human and material resources available in the pharmaceutical technology cytotoxic unit.

28 Research on the optimization of logistics in pharmaceutical enterprises

Objective In order to establish a drug supply security system standard and meet the management system need of drug circulation enterprises, we studied the pharmaceutical distribution optimization problem to reduce the cost of medicine circulation and improve the efficiency of the pharmaceutical supply chain, which includes analysis of the requirements of the hospital market, forecasts and the location of the pharmaceutical distribution centre. Methods An ELSON location model based on flow is constructed to quantitatively analyze the relationship between logistics and non-logistics elements of the drug distribution centre. A method based on linear tables and a process to determine the distribution centre of the pharmaceutical distribution unit is proposed. The EIQ analyzis method is proposed to analyze the number of drugs and the rules of mining. Results The results show that the trends in efficiency and stability were roughly stable after the proposed quantum ant swarm algorithm was executed 100 times, but the trends fluctuated more when the other three algorithms were used. The solutions were also better with the other algorithms. Conclusions This research provides theoretical support and guidance for the optimization and management of the logistics systems of pharmaceutical distribution enterprises, which can effectively reduce the cost and improve the efficiency of medicine circulation. Acknowledgments This research was financially supported by the Scientific Research Project of Liaoning Province Education Department, China (Grant No. L2014183), the National Natural Science Foundation, China (Grant No. 51579024) and the Dr Scientific Research Fund of Liaoning Province (Grant No. 201601244).

Ecological risk assessment of pharmaceuticals in the receiving environment of pharmaceutical wastewater in Pakistan

The pharmaceutical industry of Pakistan is growing with an annual growth rate of 10%. Besides this growth, this industry is not complying with environmental standards, and discharging its effluent into domestic wastewater network. Only limited information is available about the occurrence of pharmaceutical compounds (PCs) in the environmental matrices of Pakistan that has motivated us to aim at the occurrence and ecological risk assessment of 11 PCs of different therapeutic classes in the wastewater of pharmaceutical industry and in its receiving environmental matrices such as sludge, solid waste and soil samples near the pharmaceutical formulation units along Shiekhupura road, Lahore, Pakistan. Target PCs (paracetamol, naproxen, diclofenac, ibuprofen, amlodipine, rosuvastatin, ofloxacin, ciprofloxacin, moxifloxacin, sparfloxacin and gemifloxacin) were quantified using in-house developed HPLC-UV. Ibuprofen (1673µg/L, 6046µg/kg, 1229µg/kg and 610µg/kg), diclofenac (836µg/L, 4968µg/kg, 6632µg/kg and 257µg/kg) and naproxen (464µg/L, 7273µg/kg, 4819µg/kg and 199µg/kg) showed the highest concentrations among 11 target PCs in wastewater, sludge, solid waste and soil samples, respectively. Ecological risk assessment, in terms of risk quotient (RQ), was also carried out based on the maximum measured concentration of PCs in wastewater. The maximum RQ values obtained were with paracetamol (64 against daphnia), naproxen (177 against fish), diclofenac (12,600 against Oncorhynchus mykiss), ibuprofen (167,300 against Oryzias latipes), ofloxacin (81,000 against Pseudomonas putida) and ciprofloxacin (440 against Microcystis aeruginosa). These results show a high level of ecological risk due to the discharge of untreated wastewater from pharmaceutical units. This risk may further lead to food web contamination and drug resistance in pathogens. Thus, further studies are needed to detect the PCs in crops as well as the government should strictly enforce environmental legislation on these pharmaceutical units.

Personnel hygiene in pharmaceuticals: Its importance and requirements for personnel involved in the manufacturing of quality medicines

Good personal hygiene is required in pharmaceutical industries to safeguard the product and avoid any type of contamination that effects quality of medicinal product. Individual persons are responsible for quality of a medicinal product and hence collectively can be termed as “personnel”. Even though controls are in place to manage equipment, incoming raw materials or packing materials, human beings are one of the main source of contamination. It is not enough to have a high tech state of the art pharmaceutical manufacturing facility and Quality control unit to release the raw materials, it is also very much essential to have well trained personnel to operate the equipment, to manufacture the quality product and handle the pharmaceutical product at every stage in manufacturing a dosage form. Therefore, all the personnel employed by the pharmaceutical sector should be well trained and educated on the importance of personnel hygiene. In this article, the authors have tried to outline importance of personnel hygiene and opined that there is a need to stress more on this subject especially at undergraduate levels of pharmacy curriculum. If this is included at undergraduate level, it will be easy to inculcate the best practices as per Good Manufacturing Practices (GMP) for the freshers entering the pharmaceutical manufacturing sector.

The Application of Modern Powder Characterisation Methods in Product and Process Development of Solid Dosage Forms

The pharmaceutical industry still produces the vast majority of their products, from powdered ingredients, in the form of solid doses. Despite their ubiquity, powders are difficult materials to characterise and understand, as evidenced by the frequent problems encountered during manufacture. The reason for this is their complex rheological behaviour coupled with numerous environmental variations, such as humidity. Equally, the range of processes used to manipulate powders subject them to extremes of stress from high compaction loads seen in compactors to the dispersed state seen in fluidised bed dryers. Thus, it is evident that ensuring that the powders characteristics are compatible with the way they are to be processed is a clear prerequisite for today's Quality by Design driven manufacturing. Modern, computer controlled instrumental techniques, including the dynamic, bulk and shear property measurements have enabled direct measurements of a powders response to aeration, consolidation and flow rate - all at low stresses - as well as quantifying shear and bulk properties (such as density, compressibility and permeability). In order to demonstrate how fully characterising a powder can be used in the design, operation and troubleshooting of processes, this paper will present examples of common pharmaceutical unit operations and the different powder characteristics that most influence the performance of each.

PATH FINDER PROCESS VALIDATION OF MOIST HEAT STERILIZER IN PARENTRAL MANUFACTURING UNIT

Objective:- Moist heat sterilization is the most important in pharmaceutical Parentral manufacturing unit. Sterile products have several unique dosage form properties, such as freedom from microorganisms, freedom from pyrogens, freedom from particulates, and extremely high standards of purity and quality; however, the ultimate goal in the manufacture of a sterile product is absolute absence of microbial contamination. An attempt has been made in this research work to validate the Moist Heat Steriliser with technical parameters  classified as Critical and Variable Parameters. Method:- Moist Heat Sterilization method is used for Sterilization of Accessories,Garments ,Silicon tubes, filtration assembly etc. on basis of coagulation of cell proteins. Moist Heat Steriliser  is validated every half year to ensure the system is liable to consistently, provide dehydrogenated or sterile product and meets the quality standards. Validation is done by proper planning by taking regular load and experimental load of regular batches of the product. The study is done on Heat distribution, Heat penetration, and Bio burden determination, Minimize the utility cost, and Man hours during sterilization cycle. Result:- The result found in this research work leads to setting up New approach to Validate Moist Heat Steriliser in Parentral manufacturing unit with cost effective way. Conclusion:- The Path finder validation process setup through this project is Cost saving through Energy as well as Man Hour Saving and Breakage of Units also maintain Sterility in product. It is helpful to find out Hot and Cold Spots in Moist Heat sterilizer and Designing and   Placement of RTDs. The findings were submitted to the Parentral Department of Vital HealthCare Pvt. Ltd., Satpur. MIDC, Nashik. KEYWORDS:-Moist heat Sterilization , Process Validation , Critical and Variable parameters.

Commentary on Reconstituting Fibrinogen Concentrate to Maintain Blinding in a Double-blind, Randomized Trial in an Emergency Setting

BackgroundThe gold standard of trial design is the double-blind, placebo-controlled, randomized trial. Intravenous medication, which needs reconstitution by the attending clinician in an emergency situation, can be challenging to incorporate into a suitably blinded study. DiscussionWe have developed a method of blindly reconstituting and administering fibrinogen concentrate (presented as a lyophilized powder), where the placebo is normal saline. Fibrinogen concentrate is increasingly being used early in the treatment of major hemorrhage. Our methodology was designed for a multicenter study investigating the role of fibrinogen concentrate in the treatment of the coagulopathy associated with major obstetric hemorrhage. The method has been verified by a stand-alone pharmaceutical manufacturing unit with an investigational medicinal products license, and to date has successfully been applied 45 times in four study centers. There have been no difficulties in reconstitution and no related adverse events reported. ConclusionWe feel our method is simple to perform and maintains blinding throughout, making it potentially suitable for use in other trials conducted in psychologically high-pressure environments. Although fibrinogen concentrate was the focus of our study, it is likely that the method is applicable to other lyophilized medication with limited shelf life (e.g., antibiotics).

Pharmaceutical Industry: Key Issues in Growth in Pakistan & International Market

Pakistan has a very vibrant and forward-looking Pharma Industry. At the time of independence in 1947, there was hardly any pharma industry in the country. Today Pakistan has about 400 pharmaceutical manufacturing units including those operated by 25 multinationals present in the country. The Pakistan Pharmaceutical Industry meets around 70% of the country's demand of Finished Medicine. The domestic pharma market, in term of share market is almost evenly divided between the Nationals and the Multinationals (Ahmed & Saeed, 2012).The National pharma industry has shown a progressive growth over the years, particularly over the last one decade. The industry has invested substantially to upgrade itself in the last few years and today the majority industry is following Good Manufacturing Practices (GMP), in accordance with the domestic as well as international Guidance. Currently the industry has the capacity to manufacture a variety of product ranging from simple pills to sophisticated Biotech, Oncology and Value Added Generic compounds (Aamir & Zaman, 2011).Although Pakistan 's pharmaceutical and healthcare sectors are expanding and evolving rapidly, about half the population has no access to modern medicines. Clearly this presents an opportunity, but much more work needs to be done by the government and industry's stakeholders. The value of pharmaceuticals sold in 2007 exceeded US$1.4bn, which equates to per capita consumption of less than US$10 per year and value of medicines sold is expected to exceed US$2.3 B by 2012 (Ahmed et al., 2011).

Industry Perspectives on Process Analytical Technology: Tools and Applications in API Manufacturing

The IQ Consortium reports on the current state of process analytical technology (PAT) for active pharmaceutical ingredient (API) manufacturing in branded pharmaceutical companies. The article describes the application of PAT in manufacturing and provides representative examples in four common pharmaceutical unit operations: reaction and workup, crystallization, drying, and milling.

Stability of Melphalan in 0.9% Sodium Chloride Solutions Prepared in Polyvinyl Chloride Bags for Intravenous Injection.

Melphalan is an alkylating agent frequently used in an intravenous formulation to treat hematologic malignancies and solid tumors in both adults and children. According to the manufacturer, melphalan is stable in sterile 0.9 % sodium chloride for 90 min at room temperature (RT). Several authors have studied the stability of different concentrations of melphalan; however, most were not adapted to the current manufacturing process applied in pharmaceutical centralized units. This study was conducted to determine the stability of melphalan in 0.9 % sodium chloride solutions at concentrations used for intravenous injection in practice. Melphalan is commonly prepared in diluted solutions ranging from 2 to 4 mg/ml for the treatment of adult patients and at lower concentrations (down to 0.5 mg/ml) for pediatric use. Accordingly, these were the three concentrations chosen for this study. Melphalan concentrations were measured with high-performance thin-layer chromatography (HPTLC). At RT, admixtures prepared at 4 mg/ml were stable for up to 8 h without protection from light; however, at lower concentrations, such as 0.5 and 2 mg/ml, stability did not exceed 2 h. When refrigerated, melphalan was stable for 24 h at 2 mg/ml; however, at 0.5 and 4 mg/ml, the drug was not stable. Melphalan solutions present with limited stability at 0.5, 2, and 4 mg/ml and are not adapted for delayed administration in pharmaceutical centralized units. However, at 4 mg/ml and at RT, a stability of 8 h is very interesting in practice and allows sufficient time for preparation, pharmaceutical control, transport, and administration.

Designed Blending for Near Infrared Calibration

Spectroscopic methods are increasingly used for monitoring pharmaceutical manufacturing unit operations that involve powder handling and processing. With that regard, chemometric models are required to interpret the obtained spectra. There are many ways to prepare artificial powder blend samples used in a chemometric model for predicting the chemical content. Basically, an infinite number of possible concentration levels exist in terms of the individual components. In our study, design of experiments for ternary mixtures was used to establish a suitable number of blend compositions that represents the entire mixture region of interest for a three component blend. Various experimental designs and their effect on the predictive power of a chemometric model for near infrared spectra were investigated. It was determined that a particular choice of experimental design could change the predictive power of a model, even with the same number of calibration experiments.

PP.LB01.21

Objective: Modern pharmaceutical strategies in arterial hypertension, as well as in other fields, are directed toward two major apparently contrasting objectives: 1) simplification of treatment by grouping multiple drugs into single fixed-combination pharmaceutical units (including “polypill”) to improve patient adherence, and 2: personalization of therapy to tailor treatments according to specific individual aspects including pharmacogenomics. The combined fulfillment of these objectives would conceivably entail the unrealistic development of a very great variety of fixed-combination polypills, each different for drug composition and dosage. An alternative view that could combine the need for both therapy simplification and personalization may be the concept of a flexible-combination polypill. Design and Methods: In order to test this approach, we are devising a preliminary study aimed to assess the feasibility and efficacy of shifting individual patients’ treatment from multiple daily administration (multi-administration) to a single once-a-day administration (mono-administration) of the same drugs. After approval of Ethical Committee, a cross-over randomized study will be carried out for 24 weeks in 52 well controlled non complicated hypertensive outpatients under multiple therapy with at least one hypotensive drug and/or a statin and/or aspirin. Each subject will remain for an 8 weeks period on multi-administration and for another 8 weeks period on mono-administration of the same therapy; the two periods will be separated by 8 weeks to avoid a carry-over effect and their sequence will be randomized. Results: The study will provide information on the effects of mono-administration in comparison with multi-administration of the same drugs on adherence to treatment, adverse events, ambulatory blood pressure monitoring and lipid profile. Conclusions: If results will be favorable, they could prompt large scale studies following the idea of a flexible-combination polypill and addressing the various regulatory and technological issues in the path for its realization and production systems.

Potentially harmful excipients in neonatal medicines: a pan-European observational study

ObjectivesWe aimed to describe administration of eight potentially harmful excipients of interest (EOI)—parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride—to hospitalised neonates in Europe and...

Control Systems Engineering in Continuous Pharmaceutical Manufacturing May 20–21, 2014 Continuous Manufacturing Symposium

This white paper provides a perspective of the challenges, research needs, and future directions for control systems engineering in continuous pharmaceutical processing. The main motivation for writing this paper is to facilitate the development and deployment of control systems technologies so as to ensure quality of the drug product. Although the main focus is on small-molecule pharmaceutical products, most of the same statements apply to biological drug products. An introduction to continuous manufacturing and control systems is followed by a discussion of the current status and technical needs in process monitoring and control, systems integration, and risk analysis. Some key points are that: (1) the desired objective in continuous manufacturing should be the satisfaction of all critical quality attributes (CQAs), not for all variables to operate at steady-state values; (2) the design of start-up and shutdown procedures can significantly affect the economic operation of a continuous manufacturing process; (3) the traceability of material as it moves through the manufacturing facility is an important consideration that can at least in part be addressed using residence time distributions; and (4) the control systems technologies must assure quality in the presence of disturbances, dynamics, uncertainties, nonlinearities, and constraints. Direct measurement, first-principles and empirical model-based predictions, and design space approaches are described for ensuring that CQA specifications are met. Ways are discussed for universities, regulatory bodies, and industry to facilitate working around or through barriers to the development of control systems engineering technologies for continuous drug manufacturing. Industry and regulatory bodies should work with federal agencies to create federal funding mechanisms to attract faculty to this area. Universities should hire faculty interested in developing first-principles models and control systems technologies for drug manufacturing that are easily transportable to industry. Industry can facilitate the move to continuous manufacturing by working with universities on the conception of new continuous pharmaceutical manufacturing process unit operations that have the potential to make major improvements in product quality, controllability, or reduced capital and/or operating costs. Regulatory bodies should ensure that: (1) regulations and regulatory practices promote, and do not derail, the development and implementation of continuous manufacturing and control systems engineering approaches; (2) the individuals who approve specific regulatory filings are sufficiently trained to make good decisions regarding control systems approaches; (3) provide regulatory clarity and eliminate/reduce regulatory risks; (4) financially support the development of high-quality training materials for use of undergraduate students, graduate students, industrial employees, and regulatory staff; (5) enhance the training of their own technical staff by financially supporting joint research projects with universities in the development of continuous pharmaceutical manufacturing processes and the associated control systems engineering theory, numerical algorithms, and software; and (6) strongly encourage the federal agencies that support research to fund these research areas.

A Study of Pharmaceuticals in India and Kashmir Aspect

The Indian pharmaceutical industry positions among the top five countries by volume (production) and accounts for about 10% of worldwide production. The industry?s gross revenue has grown from a simple US$ 0.3 bn in 1980 to about US$ 21.73 billion in 2009-10. Stumpy cost of skilled manpower and innovation are some of the major factors taking sides of this growth. According to the Department of Pharmaceuticals, the Indian pharmaceutical industry employs about 340,000 people and an approximate 400,000 doctors and 300,000 chemists. The Indian pharmaceutical industry is disjointed with more than 10,000 manufacturers in the controlled and unplanned segments. The products manufactured by the Indian pharmaceutical industry can be generally classified into bulk drugs (active pharmaceutical ingredients - API) and formulations. Of the total number of pharmaceutical manufacturers, about 77% make formulations, while the remaining 23% make up bulk drugs. Bulk drug is an active constituent with medicinal properties, which acts as fundamental raw material for formulations. Formulations are precise dosage forms of a bulk drug or a mixture of bulk drugs. Drugs are available as syrups, injections, tablets and capsules. Based on the pharmaceutical consumer base, the Indian API manufacturing segment can be alienated into two sectors ? innovative or branded and generic or unbranded. In 2009, the worldwide generic drug market was projected to be US$ 84 billion, of which the US accounted for 42%. India‟s generic drug industry is approximate to be US$ 19 bn and it ranks third globally, contributing about 10% to global pharmaceutical production. Pharmaceutical manufacturing units are mainly concentrated in Maharashtra and Gujarat. These regions hold for about 45% of the total number of pharmaceutical manufacturing units in India. Based on the elevated value plant species, J&K has a huge potential for establishing bio-pharmaceutical industry.

Studies on the Oxidative Removal of Sodium Thiosulfate from Aqueous Solution

Thiosulfate is generated from various process industries, such as petrochemical, metallurgical, photography processing, pharmaceutical, pigment and dye manufacturing units, etc. Thiosulfate-bearing wastewater is also produced during the anaerobic treatment of wastewater. In the present work, oxidative removal of thiosulfate in the presence of UV light from aqueous solution has been investigated. The effect of thiosulfate concentration, oxygen partial pressure, UV light intensity and air flow rate on the kinetics of thiosulfate removal has been explored, and suitable rate equations were developed for the oxidation processes. 67 % of thiosulfate was removed from the aqueous solution by carrying out aerial oxidation for one hour. Using photooxidation by UV light, 1,200ppm thiosulfate could be oxidized by one hour. Overall reaction by aerial oxidation followed the second-order kinetics, whereas by photooxidation, it followed third-order kinetics.