Therapeutic Dosage Forms Research Articles

An Estimation of Baricitinib by AQbD-driven UV Spectrophotometry Development and Validation Process

Background: Baricitinib (BCTB) is a novel Janus Kinase (JAK) 1 and 2 inhibitor used in the therapy of rheumatoid arthritis, approved by the “Food and Drug Administration” in 2018. It has significant dose-dependent effectiveness and severe side effects. Thus, it is crucial to figure out its concentration in developed dosage forms. The literature search revealed that there has only been one UV spectroscopy technique documented up to this point. Methanol was chosen as the detection medium in this approach, which is not comparable with plasma or serum. As a result, the preliminary research suggested developing a UV spectroscopic approach that can estimate BCTB concentration and compare it to its concentration in the plasma or serum. Thus, in the proposed method, 7.4 pH phosphate buffer was selected as a mobile phase. Aim: Using the Analytical Quality by Design (AQbD) methodology, a simple, robust spectrophotometric method for the detection of BCTB in API form and Niosomes drug delivery system is designed and assessed. Methods: In the AQbD approach, a face-centered CCD design of Design Expert 13 software was used to evaluate two critical method variables: scanning speed and sampling interval. The design space suitability was confirmed by standard error and overlay plots. The 2-D contour and 3-D response surface plots were used to forecast the relationship between the response variable and predictor variables. Results: Baricitinib displays an absorption maximum at 249.40 nm in saline phosphate buffer pH 7.4. The distinguished linearity of the method was obtained over a concentration of 5–30 µg/ml with a correlation coefficient (R2 ) value of 0.998. BCTB % assay was found to be near 99 %. Intraday and Interday precision were found to have % RSDs of 0.067–0.488 and 0.146–0.942, respectively. Conclusion: The established spectrophotometric technique was observed to be precise as per ICH revised guidelines ICH Q2 (R1) and Q14 for analytical method validation. Our findings are instructional for the future design and development of safe and reliable therapeutic dosage forms of BCTB for rheumatoid arthritis.

Comparative stagewise mapping of trace elements using ICP-OES in five Ayurvedic Marine Drugs highlights their posologic and clinical implications

Rasashastra, an Ayurvedic pharmaceutical branch, scientifically converts natural resources into palatable therapeutic dosage forms. Ayurvedic Marine Drugs (AMD) are mainly calcium carbonate/ calcite, but in Ayurvedic treatment modality they are uniquely used for several ailments. Moreover, their detailed microchemical compositions have seldom been reported. In this study, five raw materials, conch, oyster shell, cowry, coral, and pearl, their transitions during the manufacturing process, and the final drugs were analyzed for identification and quantitation of minor elements using a validated inductively coupled plasma optical emission spectrophotometry method. All the five raw materials contained traces of Al, Ag, B, Ba, Cu, Co, Cr, Fe, Hg, Li, K, Mg, Mn, Na, Ni, Pb, S, Sr, Tl, and Zn. Interestingly, B, Co, Cr, Li, Mn, and Ni were absent in the finished products, whereas Pb and Hg exhibited a considerable decrement during the drug formation. The first three components of principal component analysis together explained 72.09% of variance. Raw AMD indicated positive factor scores, whereas their respective purified and incinerated forms exhibited negative scores. Cluster analysis derived a dendrogram typically forming incinerated AMD group but not for the raw forms. Coral with Mg as highest content was a remarkable outlier in both these analyses as compared to Na in others. In discriminant analysis of the presence/absence of elements and periodic table-based classifications, coral and pearl showed higher variation indicating as discriminants when equated with others. Periodic table-based classification was a better model for discrimination. Correlation analysis in both classifications revealed a strong correlation of conch with oyster shells and vice versa, cowry and pearl with oyster shell and a weak correlation of coral with pearl. Coral was a good predictor followed by conch, pearl, oyster shell, and cowry, sequentially, and can be considered a moderately sensitive but highly specific model. Thus, ICP-OES technique is highly precise and accurate for assessing the micro-composition of raw, in-process, and finished products to ensure their transitions, quality, and genuineness. Such characterized traditional medicines should be further investigated in depth for their mechanistic aspects.Graphical abstract

Utility of Cilefa Pink B, a foodstuff dye as a fluoro-substrate in the devising of the first facile green Molecular-mass-Related Fluorescence Sensor for quantifying amlodipine in batched material and dosage forms; content uniformity evaluation

This study introduces the first and unique Molecular-mass-Related Fluorescence Sensor as the first fluorimetric strategy for determining amlodipine. An environmentally friendly, single-step, and direct spectrofluorimetric approach was utilized to evaluate the analyte. In an acidic setting, combining the amlodipine medication and the fluorescent dye Cilefa Pink B generated an instantaneous ultra-fluorescent product. An increase in dye response after adding amlodipine was proportional to the molecular weight of the generated complex, as measured at 329 nm. was the idea ofthe applied fluorimetric analysis. The complexing process increased the molecular mass from 879.86 to 1288.739 g mol−1. The medication's range of 0.050–1.00 µg mL−1 is directly correlated with this molecular massenlargement. The ideal settings for the changeable parameters of the system were established through an analysis of the response of the amlodipine-Cilefa Pink B system. Furthermore, the developed sensor complied with ICH (International Council for Harmonization) standards. The sensitivity limits were 0.0139 µg mL−1 (for the detection limit, LOD) and 0.042 µg mL−1 (for the quantification limit, LOQ). Additionally, this method effectively recovered the drug in its original and therapeutic dosage forms. Finally, the proposed process's environmental impact was also assessed through different modern greenness evaluation tools.

EX VIVO PERMEATION STUDY OF NANOSTRUCTURED DOSAGE FORM CONTAINING MANGO SEED KERNEL EXTRACT USING FRANZ CELL

Background: mango seeds (Mangiferin indica L.) have the ability to inhibit P. acnes, S.aureus, and E. coli bacteria and inhibit inflammation, potentially for transdermal therapeutic dosage forms. The nano-emulsion dosage forms were prepared based on the SNEDDS system with nano-oil droplets containing mango seed extract. These dosage forms contributed to carrying the active ingredient deeply into the impact site, bringing the highest efficiency, but this needs to be proven. Thus, it is necessary to study the process to evaluate the permeability of these formulas to prove their availability improvement. Objectives: To assess the transdermal permeability and active substance release of nanostructured dosage forms by a validated procedure. Methods: an ex vivo experiment was designed by adding a sample to diffuse through Franz cells. In addition, to ensure the quality and effectiveness of preparations containing mango seeds, developing and validating a process for quantifying the total polyphenols in the preparation are extremely necessary. Total polyphenols were quantified by color complexing with Folin-Ciocalteu reagents, with maximum absorption at 765 nm. Results: the procedure had been validated according to the International Conference on Harmonization (ICH) on the criteria of specificity, system compatibility with RSD = 1.02%, linearity built on the concentration range of 10–50 µg/ml with R2 = 0.998, accuracy, precision with %recovery in the range of 97.73% to 102.56%. The results showed that more than 300 mg/g of polyphenol was released after 6 hours from the tested nanostructured dosage form, about 4.3 times as many as the total amount of polyphenols in the comparative cream. Conclusions: the quantification of polyphenols diffused through Franz cells helps evaluate the quality of the preparation. The procedure had been validated according to the International Conference on Harmonization (ICH) and could be applied to evaluate nanostructured dosage forms containing mango seed kernel.

Natural flavoring agents used in pharmaceutical industry

In accordance with the International Pharmaceutical Excipients Council (IPEC), excipients are any component used during the production procedure or included in a finished medicinal formulation but which is not an active ingredient or a prodrug. The USP-NF defines Forty different types of additives for usage in medicines. Another of the classes, organoleptic compliance, gives medicines flavor and color. Medicine is made more palatable by adding flavors. Again, depending on where they originate, these tastes are classified as natural, artificial, or natural and artificial (N&A). To deliver not only tastes but also a delightful flavor, flavoring agents are used in pharmaceutical preparations such edible syrup, oral suspension, herbal remedies, pills, tablets that can be chewed, bubbly tablets, easily dispersed tablets, and ODT. They are used to boost patient compliance or enhance the taste of therapeutic dosage forms.

Fabrication of Chitosan Based Antibacterial Implant for Multibacterial Bone Infection

Despite advancements in medicines and novel surgical methods, osteomyelitis is still a complex and difficult to treat multi-bacterial bone infection. It generates in tissue necrosis along with rupturing of bone in chronic cases leading towards limited vascularity at infection site, local treatment might not show accountable level of antibiotic at infection site. The present research aims towards development and evaluation of bio-degradable implant of Ciprofloxacin hydrochloride to treat local osteomyelitis. Chitosan is widely investigated biodegradable polymer with hydroxyl moiety which is active and can be altered chemically to develop biomedical and therapeutic dosage forms. Here this active group was modified using epichlorohydrin & crosslinked Chitosan matrices were used as carrier to formulate different Ciprofloxacin implant. In vivo parameters and in vitro study was conducted for optimized batch. The formulation having 40% drug loading (EC4) was found to be optimum when all evaluation parameters were tested. The concentration of Ciprofloxacin Hydrochloride (HCl) in bone and surrounding tissues is much higher than minimum inhibitory concentration (MIC) even after a month. After observing the water uptake and extended release of drug from all formulations the drug loading was found to be higher. The present work concluded that, the highly branched chitosan remarkably reduce the percent (%) drug release up to a month which could be useful in the treatment of osteomyelitis.

A brief review on pharmaceutical dissolution - interlinking the aspects of science and regulation.

Dissolution is a multistep process between the affinity of the solute and the solvent by which a solid substance interacts among the heterogeneous phases of solute -solute, solvent-solvent and the solute-solvent interface to yield a solution. In pharmaceutical industry dissolution testing of solid dosage form gives a signal of the operability of the dosage form in biological system. The rate of absorption is partially or completely controlled by the dissolution of drug from its dosage forms in the gastrointestinal tract. This vital quality control aspects also ensures batch to batch uniformity in drug release, bioavailability, and to develop efficacious therapeutic dosage forms. It also ensures to evaluate critical biopharmaceutical parameters of the dosage forms. Hence the study of dissolution is an interplay between the science and the development of regulatory profile of a dosage form for quality control aspects. The present review focuses on the science, theories, factors relevant to in vitro dissolution, and therefore the role of it’s in the pharmaceutical regulation.

Study the pharmacokinetics, pharmacodynamics and hepatoprotective activity of rosuvastatin from drug loaded lyophilized orodispersible tablets containing transfersomes nanoparticles

Rosuvastatin is a hepato-selective statin of limited water solubility and poor oral bioavailability. The rationale behind this work was to develop pullulan based freeze-dried orodispersible tablets containing rosuvastatin flexible lipid-based nanoparticles (transfersomes) to enhance rosuvastatin bioavailability and hypolipidemic activity. Drug loaded transfersomes were prepared, characterized, and loaded into pullulan based freeze-dried orodispersible tablets. The prepared tablets were evaluated for their quality attributes and in vivo disintegration time. The pharmacokinetic behavior of the prepared tablets was studied on male Wistar rats and compared to commercial drug tablets. The hypolipidemic, hepatic enzyme and antioxidant activities were also assessed in poloxamer-induced hyperlipidemic rats. Hepatotoxicity was also investigated. The developed transfersomes showed oval irregular shape vesicles and illustrated an average vesicle size of about 230.34 ± 8.73 nm, a polydispersity index value of 0.508 ± 0.075, a zeta potential value of −10.29 ± 0.46 mV and an entrapment efficiency of 78.13 ± 0.54%. The prepared tablets were complying with the pharmacopeial standards for orodispersible tablets specification. The relative bioavailability of the orodispersible tablets was found to be 133.59%. The prepared orodispersible tablets were more effective than the commercial drug product in reducing the serum lipids, and improving the hepatic enzyme and serum antioxidant levels. No remarkable histopathological changes were observed. So, pullulan based freeze-dried orodispersible tablets loaded with rosuvastatin transfersomes are an effective and safe therapeutic dosage form in treatment of hyperlipidemia, but more preclinical and clinical investigations are required.

Gamboge Resin-Based Phase Separation <i>In Situ</i> Forming Gel

Abstract. The in situ forming gel (ISG) has been developed as a controlled drug delivery system to prolong drug release. This study aims to prepare ISG system based on gamboge resin (GB) as matrix former. The various amounts of GB dissolving in dimethyl sulfoxide (DMSO) and N-methyl pyrrolidone (NMP) were used to obtain the ISG systems and evaluated for their pH, viscosity, injectability and matrix forming. The antimicrobial activities against three strains of Staphylococcus aureus including the Methicilin Resistant S. aureus (MRSA) and Porphyromonas gingivalis were conducted. GB ISG systems exhibited good injectability with low viscosity. GB in DMSO showed a faster transformation to solid matrix compared to that in NMP. The gambogic acid (GA) content in crude GB was 33.70 ± 0.13%. The sustainable GA release from GB ISG could be attained. Thus, GB ISG exhibits the potential application as a drug delivery system for active compounds and is enable for using as a therapeutic dosage form owing to its antimicrobial activity.

Stable Cocrystals and Salts of the Antineoplastic Drug Apatinib with Improved Solubility in Aqueous Solution

Apatinib (APA) belongs to the targeted antineoplastic family of drugs by inhibiting the vascular endothelial cell growth factor receptor (VEGFR-2) of tyrosine kinase. APA encounters poor aqueous solubility problems, and its therapeutic dosage form, apatinib mesylate (ATM), is unstable and dissociates completely to APA in aqueous solution. Here, we synthesized and evaluated three new cocrystals of APA with adipic acid (APA + ADA), sebacic acid (APA + SEA), and d/l-mandelic acid (APA + d/l-MA), and four new salts with succinic acid (APA + SUA-H2O), salicylic acid (APA + SA), 1-hydroxy-2-naphthoic acid (APA + HNA), and saccharin (APA + SAC). All the solid forms were characterized by powder X-ray diffraction, infrared spectroscopy, differential scanning calorimetry, and dynamic vapor sorption. The molecular components and structures were confirmed by single crystal X-ray diffraction. APA + SEA is able to overcome the instability problem and has improved solubility compared with ATM. Hence, APA + SEA has the p...

The Application of Medicinal Plants in Traditional and Modern Medicine: A Review of <i>Thymus vulgaris</i>

Medicinal plants have played an essential role in the development of human culture. Medicinal plants are resources of traditional medicines and many of the modern medicines are produced indirectly from plants. This study illustrates the importance of traditional and modern medicines in the treatment and management of human diseases and ailments. It has been confirmed by WHO that herbal medicines serve the health needs of about 80 percent of the world’s population; especially for millions of people in the vast rural areas of developing countries. Meanwhile, consumers in developed countries are becoming disillusioned with modern health care and are seeking alternatives. Thymus vulgaris is a species of flowering plant in the mint family Lamiacea. Thymus is a widely used medicinal plant in food and pharmaceutical industries. Among different species of Thymus, Thymus vulgaris is used more than other species in therapeutic dosage forms. In Traditional medicine T. vulgaris is cultivated in many countries by most people especially in rural areas depending on herbal medicines to treat many diseases including inflammation-related ailments such as rheumatism, muscle swelling, insect bites, pains, etc. Also the modern medicine in essential oil of thyme has demonstrated that the compounds have shown anti-inflammatory, antioxidant, antibacterial and antifungal properties. In this review the objective is to consider the past and present value of medicinal plants such as Thymus vulgar is used in traditional and modern medical practices as bioactive natural compounds.

Methodology of creating an encapsulated dosage form with bee products. Report II

On the basis of experimental studies the authors have demonstrated that a topical issue of the pharmaceutical science today is development of the rational therapeutic dosage forms based on standardized biologically active substances of bee products that have specific chemical and pharmacological properties for new domestic, natural, highly effective drugs for prevention and treatment of ulcer diseases of the human gastroduodenal area. The pharmaceutical market of drugs with the antiulcer activity of different dosage forms has been analyzed. It has been found that dosage forms produced in a small range are economically and socially efficient for further development of a completely new drug based on bee products. Today science has proven that encapsulated dosage forms are promising. This dosage form is a cost effective, and allows to encapsulate various drugs from substances in the solid state to liquid and pasty ingredients. Research in recent years has confirmed that the choice of a rational dosage form of drugs in combination with excipients provide the optimal pharmacological effect of drugs under development, which production is possible both in industrial and pharmacy conditions.

Pharmaceutical applications of biocompatible polymer blends containing sodium alginate

AbstractBiocompatible polymer blends, such as alginate blends, have a widespread use in pharmaceutical and medical applications due to their specific features, such as biodegradation, adhesiveness, and thermo‐ and pH sensitivity and that can be obtained from the mixture composition. In this work, the use of alginate blends was tested in a novel production methodology of therapeutic dosage forms based on polymeric chain reticulation phenomena induced by exposure to bivalent ions. Two kinds of sodium alginate were used to obtain gel films (structured films) in blends with Pluronic F127®. The blends were considered for applications in gel paving of drug‐eluting stents. Sodium alginate was also used in shell–core particle production (structured particles) to obtain shell‐barrier reducing drug release in the preparative steps (see wash operations). Both structures, films and particles, were obtained using Cu2+ and Ca2+ ions, respectively. Film/shell barrier properties were tested in dissolution experiments using vitamin B12 as an active molecule model. Experimental work demonstrated that the alginate composition is a crucial point in defining reticulated structures. © 2012 Wiley Periodicals, Inc. Adv Polym Techn 31: 219–230, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/adv.21276

Classical and contemporary contrive of Varti Kalpana

Varti Kalpana was in vogue since prehistoric period. Contemporary suppositories are a slight modification of this ancient formulation. Ancient and modern literatures have advocated similar shapes and nearly same routes for administration of Vartis (except Vrana Varti ). This formulation is required for the treatment of vital parts and is associated with various important therapeutic activities. A suppository is a medicated solid dosage form intended for use in the rectum, vagina, and to a lesser extent, the urethra. Medicinal plants are huge repertory of innumerable bioactive molecules. They can be traced for their therapeutic potentials and converted into various dosage forms for convenience of treatment. Therefore, recent advances can be utilized for moulding Varti into suppository and enhancing the horizons of therapeutic dosage forms

Studies on influence of process variables on performance of gliclazide mucoadhesive microcapsules

Microencapsulation is a unique technique of controlled drug delivery system and is of major importance for effective alteration of drug release required to produce a novel formulation with desired characteristics to overcome the disadvantages of the conventional therapeutic dosage forms. Microcapsules offer efficient absorption and enhanced bioavailability owing to their higher surface area, however, mucoadhesive microcapsules render more intimate contact with the mucus membrane thereby leading to increase in the gastro intestinal residence time. Gliclazide is an oral hypoglycemic second generation sulfonyl urea, which is useful for a long-term treatment of non-insulin dependent diabetes mellitus. In the present investigation, the gliclazide microcapsules are formulated to control the release rate and improve the absorption across gastrointestinal membrane by employing ionic gelation method.The effect of various process variables such as curing time, stirring speed, stirring time, volume and concentration of curing reagent on entrapment efficiency, and drug release rate was studied. The microcapsules were evaluated for drug content, encapsulation efficiency, in vitro drug release studies. The optimized formulation was selected based on the entrapment efficiency and drug release rate.The optimized formulation of gliclazide microcapsules were evaluated for rheological properties, moisture content, swelling index, erosion studies, wall thickness and in vitro wash off test. The microcapsules formulated with 2:1 coat:core ratio by using 150 ml of 0.1M Cacl2 solution as curing reagent, at a stirring speed of 400 rpm for 60 minutes and a curing period of 48 hrs were found to be the optimum formulation. The drug release followed zero order kinetics and was controlled by peppas mechanism. The pharmacodynamic activity of optimized gliclazide microcapsules was conducted by measuring blood glucose levels in healthy albino rabbits. The percentage glucose reduction was calculated and the data was treated statistically. The hypoglycemic activity was extended up to 10 hours in case of microcapsules.

Characterization and stability of various liposome-encapsulated enoxacin formulations.

The necessity for antibacterial agents with greater intracellular efficacy has led to the development of endocytosable drug carriers such as liposomes. Enoxacin was selected as a model drug incorporated in various liposome formulations as a therapeutic dosage form using the ethanol injection method and freeze-drying. Liposomal behavior after preparation and stability test was characterized by determining the physicochemical properties of enoxacin encapsulation percent, vesicle size and turbidity. The non-phospholipid formulation of stratum corneum liposomes showed the highest encapsulation efficiency after preparation among nine liposomal formulations. The addition of dissacharides in liposomes also enhanced the encapsulation of enoxacin due to the protection of phospholipid bilayers during the freeze-drying process. The liposomes with negatively charged component and dissacharides showed lower enoxacin leakage after five weeks of storage at 45 degrees C, suggesting these formulations have high stability in long-term storage. The negative liposomes showed a different behavior than others in their decrease of size and turbidity during storage, possibly due to high surface charges of the negative formulation. Cholesterol stabilized bilayers interacted with plasma and high density lipoprotein (HDL) retained enoxacin in the vesicles. Nevertheless, liposomes with cholesterol caused a hydrolysis problem after incubation with normal saline. The formulation with trehalose not only showed high stability in storage but also in plasma and HDL. This suggested trehalose was useful to incorporate with phospholipids to produce a highly encapsulated and stabilized liposomes of enoxacin. This study also demonstrated that thought is required in utilizing turbidity as a direct index of liposomal vesicle size.

Importance of skin temperature in the regulation of sweating.

Human sweating regulation at rest, evaluating thermal inputs effects on thermoregulatory center and internal hypothalamic and skin temperatures