Selection Of Dosage Form Research Articles

Alternatives to Conventional Topical Dosage Forms for Targeted Skin Penetration of Diclofenac Sodium.

Skin penetration of an active pharmaceutical ingredient is key to developing topical drugs. This penetration can be adjusted for greater efficacy and/or safety through the selection of dosage form. Two emerging dosage forms, cream-gel and gel-in-oil emulsion, were tested for their ability to deliver diclofenac into the skin, with the target of maximising skin retention while limiting systemic exposure. Prototypes with varying amounts of solvents and emollients were formulated and evaluated by in vitro penetration testing on human skin. Cream-gel formulas showed better skin penetration than the emulgel benchmark drug even without added solvent, while gel-in-oil emulsions resulted in reduced diffusion of the active into the receptor fluid. Adding propylene glycol and diethylene glycol monoethyl ether as penetration enhancers resulted in different diclofenac penetration profiles depending on the dosage form and whether they were added to the disperse or continuous phase. Rheological characterisation of the prototypes revealed similar profiles of cream-gel and emulgel benchmark, whereas gel-in-oil emulsion demonstrated flow characteristics suitable for massaging product into the skin. This study underlined the potential of cream-gel and gel-in-oil emulsions for adjusting active penetration into the skin, broadening the range of choices available to topical formulation scientists.

HPLC-fluorescence detection for stability of harringtonine, and identification of degradation products by UPLC-Q-TOF-MS

Harringtonine (HT) is an anticancer alkaloid early extracted and isolated from cephalotaxus fortunei Hook. f., also has various pharmacological activities such as antiviral, antibacterial, antimalarial, anti-inflammatory, antioxidant, herbicidal and insecticidal. However, the factors affecting the stability of HT, the main degradation sites and mechanisms involved in its disposal process in vivo have not yet been elucidated. This study utilized HPLC-fluorescence detection method to establish a simple quantitative detection method for HT with good accuracy, precision, and high sensitivity. Temperature and pH were the main factors affecting the stability of HT, which underwent significant degradation in high temperature and alkaline environments because of the occurrence of hydrolysis reactions. In isolated biological homogenates of SD rats, except gastrointestinal tract, HT was degraded in other sites, especially respiratory, mainly in airway and lungs, and systemic metabolism, mainly in livers, spleens, and kidneys. Through UPLC-Q-TOF-MS, three forced degradation products were identified as 4′-demethyl HT, cephalotaxine, and dehydrated HT, respectively. However, the degradation product in isolated biological homogenates of SD rats was only 4′-demethyl HT due to the relatively mild environment. Our findings contributed to a necessary study basis for HT in terms of structural optimization, dosage form selection, storage and transportation.

Insights into various approaches of Phytosomes for Enhanced Therapeutic Potential of Bioactives

Efficient delivery of phytoconstituents is almost challenging task for scientific community owing to predominantly imbalanced hydrophilicity and lipophilicity considerations. Phytoconstituents are mainly hydrophilic and reveal large molecular size which exhibit less absorption and poor bioavailability. Vesicular systems for instance phytosomes are recognized as unique and novel approach to enhance solubility and bioavailability of phytoconstituents and herbal extracts. These are complexed form of phytoconstituents and phospholipid molecules which are also called as phytophospholipid complex or herbosomes. Phytophospholipid complex has shown enhanced pharmacokinetic as well as pharmacodynamic properties in comparison to conventional dosage forms. Different methods have been utilized across the globe for phytosomes preparation such as solvent evaporation, anti-solvent precipitation, co-solvent lyophilization etc. The present review focuses on various approaches commonly employed in the preparation of phytosomes. Significant attributes, characterization aspects along with selection of dosage form for phytosomes have also been highlighted.

Selection of Suitable Dosage Form in the Treatment and Management for Onychomycosis by Implementing Analytical Hierarchy Process

Onychomycosis is a significant nail disorder due to fungal infection, that causes damage to the finger or toenails. The infection involves the invasion of fungi into nail components like nail matrix, nail bed and nail plate. So the management of onychomycosis is necessary as it causes a negative impact on patients quality of life. The consequences of the disease include pain and disfigurement which in turn leads to burning, vesicle formation or stinging around the nails. The selection of topical treatment methods is a challenge for the dermatologist to achieve effective management of onychomycosis. The study aimed to benefit the dermatologist to select the best dosage form for the treatment by using the Analytical Hierarchy Process -a multicriteria decision-making tool. The various dosage forms available are for the Transungual route includes Nail lacquer, Nail patches, colloidal carriers, Nanoemulsions, Nanoparticles, Liposomes, Microemulsions, Hydrogels/In situ gels. The parameters that help to achieve the reproducibility and consistency for treatment are Drug permeation, Drug distribution, Treatment methods, Therapeutic efficacy, Patient compliance, Treatment strategy. So, it is necessary to incorporate all the factors that influence the dosage form selection in the decision-making process. Due to the side effects of oral antifungal therapies, the various transungual dosage form alternatives selected for the study are Nail patches, Nail lacquers, Nanoemulsions, Microemulsions and in-situ hydrogels. The ultimate ranking of the alternative is based on the composite score. These findings will enable the dermatologist to develop an adequate treatment strategy for the proper management of onychomycosis to improve the quality of life in patients.

Characterization of Oxidative Degradation Product of Canagliflozin by LC-MS/MS

Prior knowledge of chemical stability of drugs directs path for right selection of dosage form, excipients, storage conditions and packaging material. Literature survey revealed that, there are analytical methods reported for quantification and stability indication of Canagliflozin in bulk and formulation. But there is not much information available about the degradation products generated under different stability conditions. With this background, characterization of oxidative degradation product of Canagliflozin was successfully carried out by Liquid Chromatography-Mass Spectrometry (LC-MS/MS) studies. Degradation product was generated by forced degradation, according to International Conference on Harmonization (ICH) guidelines. Degradation product was separated from Canagliflozin by validated reverse phase (RP)-HPLC method using C18 column and Acetonitrile: Water pH 3.0 adjusted with 0.1% formic acid (70: 30, v/v) as mobile phase at a flow rate of 1mL/min. The developed RP-HPLC method was validated for different parameters as per ICH guidelines. The method was found to be linear in a range of 25-225 μg/mL. The developed method was found to be specific, accurate, precise, sensitive and robust. The marketed tablet formulation was analyzed by the developed method and the percent drug content was found to be 100.09 ± 1.96 % w/w. Separated degradation product was characterized by LC-MS/MS studies. From LC-MS/MS data probable structure of the degradation product was interpreted and the mechanism of degradation was proposed. The probable structure of degradation product was proposed as2-(4-Fluorophenyl)-5-({2-methyl-5-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]phenyl}methyl) thiophene-1-one. The mechanism of degradation was proposed by S-oxidation of thiophene ring to form thiophene oxide. This information will help synthetic chemists to design a synthesis scheme for the oxidative degradation product, which can be used as a reference standard for impurity profiling. It is also suggested to protect CN from oxidative conditions for improved stability.

Optimization of Water Guarantee for Making Face Cleaning Soap

Facial cleansers generally have good cleaning power. Facial cleansing soap is also very necessary to keep facial skin clean and healthy. One of the natural ingredients that can help the cleaning process is guava leaf water. Guava leaf water contains several secondary metabolites, such as tannins, triterpenoids, glycosides and flavonoids. In addition, the selection of dosage forms also affects the cleaning power of a cleaning soap. Therefore, in this study, a cleaning soap was made from guava leaf water and a physical evaluation of the soap was carried out in accordance with the specifications and requirements specified. The principle of the saponification reaction is the reaction between oil and KOH/NaOH. The facial cleansing soap made in this study is solid soap. Based on the quality test results, solid leri soap has a pH of 10.3, the saponification rate is 32 water content 34 water content 34% and respondent tests on the aroma and foam aspects which show good enough results so that guava water treatment can be an alternative solution to prevent the use of water. Facial cleanser that contains harmful chemicals.

Practical and operational considerations related to paediatric oral drug formulation: An industry survey

For over 15 years, US and EU regulations ensure that medicines developed for children are explicitly authorised for such use with age-appropriate forms and formulations, implying dedicated research. To shed light on how these regulations have been adopted by pharmaceutical companies and how various aspects of paediatric oral drug formulation development are currently handled, an exploratory survey was conducted. Topics included: general company policy, regulatory aspects, dosage form selection, in-vitro, in-silico and (non-)clinical in-vivo methods, and food effects assessment. The survey results clearly underline the positive impact of the paediatric regulations and their overall uptake across the pharmaceutical industry. Even though significant improvements have been made in paediatric product development, major challenges remain. In this respect, dosage form selection faces a discrepancy between the youngest age groups (liquid products preference) and older subpopulations (adult formulation preference). Additionally, concerted research is needed in the development and validation of in-vitro tools and physiology based pharmacokinetic models tailored to the paediatric population, and in estimating the effect of non-standard and paediatric relevant foods. The current momentum in paediatric drug development and research should allow for an evolution in standardised methodology and guidance to develop paediatric formulations, which would benefit pharmaceutical industry and regulators.

A REVIEW: ANTI-CANCER NATURAL PRODUCT DRUG DELIVERY SYSTEM DOSAGE FORM AND EVALUATION

A drug delivery system is a system in which a drug is released from a pharmaceutical dosage form to achieve the desired pharmacological effect. The system consists of conventional and new drug delivery systems. In the new drug delivery system, polymers are used as a matrix. The aim of this article is to find out and understand the formulation and evaluation of natural ingredients that have anticancer activity with different dosage forms and the basis for developing these dosages. Journal searches in this review came from primary data sources on the internet. Journal searches were carried out using a search engine such as Google Scholar, PubMed, and ScienceDirect. In recent years, natural products, such as extract, fraction, and isolate, are getting attention to help treat cancer. Because of their low solubility and bioavailability, the effectiveness tends to be lower than synthetic drugs. Therefore, a dosage form with a new drug delivery system was made to overcome the problem. The dosage forms commonly made are patch, suspension, powder, and emulsion with a new drug delivery system. To ensure the product that has been made met the requirements, they need to be evaluated with various methods like In vitro Study, morphology study, particle size study, and others. Cancer treatment using the natural product can be delivered through several dosage forms like patch, suspension, powder, and emulsion, with specific formulation and manufacturing methods based on several considerations such as natural ingredients properties, dosage form selection, excipient properties, and the purpose of the formulation. Dosage forms that has been made are then evaluated using several evaluation methods.

Development of Generic Drug Products by Pharmaceutical Industries Considering Regulatory Aspects: A Review

Development of generic drug product by pharmaceutical industry is a scientific and technical approach which is totally different from developing a reference or innovator product. Most of the developing countries focus on developing the generic drug products because huge amount of investment is required for innovation and to develop reference product. The generic medicine has to be bioequivalent to the innovator drug and ensure the same biological effect with proper safety and efficacy. Nowadays, the pharmaceutical industries focus on the development of generic product as this does not require that much time and cost compared to the innovator company. But development of generic product is also difficult as it contains the same therapeutic efficacy as innovator. The development approach is based on the target market, i.e. US market, EU market. If a manufacturer targets the US market, then all excipients should be USP grade, analysis should be conducted by USP method or in-house method and stability studies as well. Prior and during the development of generic drug product API selection, dosage form selection, reference product selection and characterization, formulation development, analytical method development, tech transfer or submission batch are prime concern. Then again, bioequivalence study, drug registration procedure and commercialization of the generic product considering regulatory guidance of respective regulatory agencies and the approaches taken by the regulatory agencies for the development of registration of generic medicines are also crucial as well for the development of generic drug product. The aim of this study was to review the entire stage of a generic drug development by a generic pharmaceutical company.

Relationship between selection of dosage forms of vitamin D receptor activators and short-term survival of patients on hemodialysis

Background The benefits of vitamin D receptor activators (VDRAs) for patients with chronic kidney disease are well recognized. However, the optimal criteria for patient selection, dosage forms, and duration providing the highest benefit and the least potential risk remain to be confirmed. Materials and methods The study population was derived from the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis, a multicenter prospective cohort study of 1520 incident dialysis patients. According to the VDRA usage status in March 2015 (interim report), the 967 patients surviving after March 2015 were classified into three groups: without VDRA (NV, n = 177), oral VDRA (OV, n = 447), and intravenous VDRA (IV, n = 343). Mortality rates were compared using the log-rank test, and factors contributing to all-cause mortality were examined using both univariate and multivariate Cox proportional hazard regression analyses. Results There were 104 deaths (NV, n = 27; OV, n = 53; IV, n = 24) during the follow-up period (1360 days, median), and significant differences in cumulative survival rates were observed between the three groups (p = 0.010). Moreover, lower all-cause mortality was associated with IV versus NV (hazard ratio, 0.46 [95% confidence interval 0.24–0.89]; p = 0.020). Conclusion This study demonstrated the impact of the VDRA dosage form on the short-term survival of incident hemodialysis patients during the introduction period. Our results suggest that relatively early initiation of intravenous VDRA in patients beginning hemodialysis may have some clinical potential.

Potentially Inappropriate Prescribing of Oral Solid Medications in Elderly Dysphagic Patients.

Pharmaceutical formulations suitable for dysphagic patients are not always commercially available, motivating caregivers to crush tablets or open capsules to facilitate swallowing. Since this action may modify the characteristics of the medicine, it should be considered potentially inappropriate. This paper is the first to focus on how hospitalization affected the rate of potentially inappropriate prescriptions (PIPs) and the incidence of dosage form-related PIPs in elderly patients with dysphagia. Data was collected by reviewing patient medical records in the Italian National Research Center on Aging of Ancona. The therapy at admission and discharge was analysed in terms of: inappropriate drug associations, inappropriate drugs for dysphagic patients, inappropriate dosage forms and inappropriate dosage form modifications. Forty-one dysphagic patients with an average age of 88.3 years were included in the study and 451 prescriptions were analysed. PIPs were widespread at admission, and hospitalization did not improve the situation in a statistically significant manner. The most common PIPs identified (>80%) were related to dosage form selection and modification. This study highlights a clear need for continuing medical education about prescription appropriateness and modification of solid dosage forms in patients with dysphagia.

Biorelevant drug release of Metformin dosage forms using complementary in vitro tools

Drug release from immediate release (IR) and extended release (ER) metformin products was investigated using the Dow Chemical Company’s FloVitroTM biorelevant dissolution instrument. This was complemented by using the Sirius SDi2 (Surface Dissolution Imaging) platform to investigate mechanistic differences accounting for drug release. Level A IVIVC was demonstrated for metformin IR dosage forms, using FloVitroTM, whilst ER tablets demonstrated lower Cmax and Tmax using the same method. The SDi2 showed disintegration as the main release mechanism for IR tablets, whilst swelling and drug diffusion was observed for ER tablets. FloVitroTM and SDi2 technologies can be used to compare behaviour of formulations during dosage form selection

Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis

Knowledge about the region-specific absorption profiles from the gastrointestinal tract of orally administered drugs is a critical factor guiding dosage form selection in drug development. We have used a novel approach to study three well-characterized permeability and absorption marker drugs in the intestine. Propranolol and metoprolol (highly permeable compounds) and atenolol (low-moderate permeability compound) were orally co-administered to rats. The site of drug absorption was revealed by high spatial resolution matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and complemented by quantitative measurement of drug concentration in tissue homogenates. MALDI-MSI identified endogenous molecular markers that illustrated the villi structures and confirmed the different absorption sites assigned to histological landmarks for the three drugs. Propranolol and metoprolol showed a rapid absorption and shorter transit distance in contrast to atenolol, which was absorbed more slowly from more distal sites. This study provides novel insights into site specific absorption for each of the compounds along the crypt-villus axis, as well as confirming a proximal-distal absorption gradient along the intestine. The combined analytical approach allowed the quantification and spatial resolution of drug distribution in the intestine and provided experimental evidence for the suggested absorption behaviour of low and highly permeable compounds.

Polypharmacy and enteral nutrition in patients with complex chronic diseases

Oral medications are often administered through enteral feeding tubes in patients with complex chronic diseases. It is important to consider possible interactions between drugs and enteral nutrition that might lead to unsuccessful treatment or tube occlusion. These patients become subjects for higher risk of problems and errors such as drug incompatibility with enteral nutrition and inappropriate dosage form selection. It is possible to minimize the risk of tube occlusion and incompatibilities problems by recognizing potential medication errors, selecting the most appropriate drug and dosage form and using appropriate administration techniques. In this context, high-alert medications for patients with chronic diseases deserve special attention. Furthermore, risk exposure should be considered among healthcare professionals and patient caregivers handling hazardous drugs. Therefore, main incompatibility problems between drugs and enteral nutrition have been reviewed, including general recommendations for administration of oral medications through enteral feeding tubes and safe handling of hazardous drugs. Specific recommendations for administration of high-alert medications for patients with chronic diseases are also included.

Reflection on the Pharmaceutical Formulation Challenges Associated with a Paediatric Investigation Plan for an Off-Patent Drug.

In Europe, the development of pediatric medicines for new patent protected products is mandatory and applicants are required to submit a Paediatric Investigation Plan (PIP) to the regulatory authorities. The process is voluntary for off-patent medicines and despite the availability of incentives, there is still a huge unmet need for the development of off-patent pediatric medicines. The aim of the EU grant funded "Labeling of Enalapril from Neonates to Adolescents" (LENA) project is to develop a new pediatric dosage form of the off-patent drug enalapril, for the treatment of heart failure in patients aged from birth to 18years. This article provides an overview of some of the key formulation challenges that were faced during the product development programme and PIP process, including selection of dosage form and excipients, methodology for administration of the product and evaluation of patient acceptability.

Thermodynamics of Water–Solid Interactions in Crystalline and Amorphous Pharmaceutical Materials

Pharmaceutical materials, crystalline and amorphous, sorb water from the atmosphere, which affects critical factors in the development of drugs, such as the selection of drug substance crystal form, compatibility with excipients, dosage form selection, packaging, and product shelf-life. It is common practice to quantify the amount of water that a material sorbs at a given relative humidity (RH), but the results alone provide minimal to no physicochemical insight into water-solid interactions, without which pharmaceutical scientists cannot develop an understanding of their materials, so as to anticipate and circumvent potential problems. This research was conducted to advance the science of pharmaceutical materials by examining the thermodynamics of solids with sorbed water. The compounds studied include nonhygroscopic drugs, a channel hydrate drug, a stoichiometric hydrate excipient, and an amorphous excipient. The water sorption isotherms were measured over a range of temperature to extract the partial molar enthalpy and entropy of sorbed water as well as the same quantities for some of the solids. It was found that water-solid interactions spanned a range of energy and entropy as a function of RH, which was unique to the solid, and which could be valuable in identifying batch-to-batch differences and effects of processing in material performance.

A benefit/risk approach towards selecting appropriate pharmaceutical dosage forms – An application for paediatric dosage form selection

The design and selection of new pharmaceutical dosage forms involves the careful consideration and balancing of a quality target product profile against technical challenges and development feasibility. Paediatric dosage forms present particular complexity due to the diverse patient population, patient compliance challenges and safety considerations of this vulnerable population.This paper presents a structured framework for assessing the comparative benefits and risks of different pharmaceutical design options against pre-determined criteria relating to (1) efficacy, (2) safety and (3) patient access. This benefit/risk framework has then been applied to three hypothetical, but realistic, scenarios for paediatric dosage forms in order to explore its utility in guiding dosage form design and formulation selection. The approach allows a rigorous, systematic and qualitative assessment of the merits and disadvantages of each dosage form option and helps identify mitigating strategies to modify risk.The application of a weighting and scoring system to the criteria depending on the specific case could further refine the analysis and aid decision-making. In this paper, one case study is scored for illustrative purposes. However, it is acknowledged that in real development scenarios, the generation of actual data considering the very specific situation for the patient/product/developer would come into play to drive decisions on the most appropriate dosage form strategy.

Effectiveness of Ruyijinhuangsan on phlebitis induced by vinorelbine and optimization of its formulations and selection of dosage forms

Objective: To investigate preventive and therapeutic effects of Ruyijinhuangsan on phlebitis induced by vinorelbine,select dosage forms and optimize the formulations.Methods: The phlebitis model of mice was established by injection of vinorelbine via tail vein.The occurrence and relief of tail swelling were as effectiveness index in mice.Different formulations by uniform designed based on traditional Chinese medical theory were examined in different groups.Results: Cataplasm group which consisted of rhubarb,common turmeric rhizome and maculatum etc(group D),Ruyijinhuangsan cataplasm made by ourselves(group G),cataplasm which consisted of rhubarb,amur cork-tree and officinal magnolia bark etc(group F) and its gel(group F3),cataplasm of Ruyijinhuangsan at market(group I) were all effectiveness and group F3 was more effective than the other groups.Conclusion: Ruyijinhuangsan has a distinct curative effect on the infusion phlebitis induced by vinorelbine.There is difference between different prescriptions and dosage forms.The optimal prescriptions could improve the efficacy and it need further study in clinic.

Improvement Activities for Appropriate Selection of Dosage Form of Drugs Administered via Enteral Feeding Tube

Improvement Activities for Appropriate Selection of Dosage Form of Drugs Administered via Enteral Feeding Tube

Pharmaceutical Devices for Oral Cavity-based Local and Systemic Drug Delivery

ABSTRACT − Pharmaceutical technology has primarily focused on the development of the best dosage forms dependingon the route of administration. The design of dosage forms is greatly influenced by the route of administration. Due to avariety of advantages such as avoidance of first-pass effect, abundant blood supply and easy access to the absorption site,the oral cavity has frequently been selected as a site for drug delivery. Since the oral cavity is relatively unique from theanatomical and physiological viewpoint, one should always consider these conditions when designing the drug delivery sys-tems for the oral cavity. In this regard, the current review paper was prepared to summarize the essential features of the drugdelivery systems utilized in the oral cavity, along with the introduction of various dosage forms developed to date.Key words − Oral cavity, Buccal, Bioadhesive, Mucoadhesive, Drug delivery system, Dosage forms A number of buccal delivery systems are being investigatedand have been used for drug absorption via the oral mucosa.These include aqueous solutions (e.g. mouth wash, a dose ≤25 mL), conventional buccal and sublingual tablets, liquid-filled capsules, adhesive tablets, adhesive gels, adhesivepatches, chewing gums, metered-dose aerosols and devicesattached to the teeth or implanted in the tooth enamel (Merkleet al., 1990). The selection of dosage form primarily relies onthe therapeutic intention, such as rapid or prolonged effect andsystemic or local therapeutic effect, as well as the physico-chemical properties of the drug molecules. It would be addi-tionally important to increase the patient acceptability of thedelivery system i.e. ease of use and avoidance of discomfort.Karsenty et al. (1994) have evaluated clinically the patientacceptance of a transmucosal patch (a matrix of polyacrylicacid and polyisobutylene with adhesive impermeable backinglayer) with regard to comfort, irritation and feeling when pre-sented and removed. They reported that it is important to dem-onstrate patient acceptance if the delivery system is to gain awide range of applicability for a number of therapies. It is alsoimportant that the additives used to formulate oral mucosaldosage forms do not stimulate salivary secretion as this maycause the loss of a large fraction of the active ingredient priorto absorption. Rathbone et al. (1994) have reported that thesize, shape and the thickness of the delivery system should beconsidered to maximise patient compliance. Anders andMerkle (1989) have proposed the appropriate dimensions ofdosage forms for buccal use. For an inflexible conventionaltablet, 5-8 mm in diameter is suitable for comfort and the abil-ity of the patient to constantly detect its presence. In the caseof a flexible patch, the maximum size would be 10-15 cm