Application of Plackett-Burman design for screening of factors affecting pitavastatin nanoparticle formulation development.

INTRODUCTION: Nanoparticle formulation of pitavastatin calcium is a potential alternative to solve the solubility related problem. However, the formulation of nanoparticle involves various parameters that affect product quality. Plackett-Burman design could facilitate an economical experimental plan that focuses on determining the relative significance of many. AIM: The objective of this study was to screen the variables which could significantly affect the pitavastatin nanoparticle formulation. MATERIALS AND METHODS: The pitavastatin nanoparticles were formulated by preparing nanosuspension using the emulsion solvent evaporation technique followed by freeze-drying. A Plackett-Burman screening design methodology was employed in which seven factors at two levels were tested at 12 runs to study the effect of formulation and process variables on particle size and polydispersity index of nanoparticles. The surface morphology and crystalline nature of nanoparticle were also evaluated. RESULTS: The particle size and polydispersity index of nanosuspension was found in the range of 113.1 to 768.5 nm and 0.068 to 0.508, respectively. Statistical analysis of various variables revealed that stabilizer concentration, injection flow rate, and stirring rate were the most influential factors affecting the particle size and polydispersity index of the formulation. X-ray diffraction (XRD) and scanning electron microscopy (SEM) study suggested the amorphous nature of nanoparticles. CONCLUSIONS: This study concluded that the Plackett-Burman design was an efficient tool for screening the process and formulation variables affecting the properties of pitavastatin nanoparticles and also for the identification of the most prominent factor.

Current knowledge on biodegradable microspheres in drug delivery.

INTRODUCTION: Biodegradable microspheres have gained popularity for delivering a wide variety of molecules via various routes. These types of products have been prepared using various natural and synthetic biodegradable polymers through suitable techniques for desired delivery of various challenging molecules. Selection of biodegradable polymers and technique play a key role in desired drug delivery. AREAS COVERED: This review describes an overview of the fundamental knowledge and status of biodegradable microspheres in effective delivery of various molecules via desired routes with consideration of outlines of various compendial and non-compendial biodegradable polymers, formulation techniques and release mechanism of microspheres, patents and commercial biodegradable microspheres. EXPERT OPINION: There are various advantages of using biodegradable polymers including promise of development with different types of molecules. Biocompatibility, low dosage and reduced side effects are some reasons why usage biodegradable microspheres have gained in popularity. Selection of biodegradable polymers and formulation techniques to create microspheres is the biggest challenge in research. In the near future, biodegradable microspheres will become the eco-friendly product for drug delivery of various genes, hormones, proteins and peptides at specific site of body for desired periods of time.

Development and optimization of modified release IPN macromolecules of oxcarbazepine using natural polymers.

The study shows development and optimization of modified release interpenetrating polymer network (IPN) macromolecules (beads) of oxcarbazepine using sodium alginate-egg albumin prepared by ionotropic gelation method and CaCl2 as a cross-linker. Independent variables were identified based on preliminary study of investigation. The effect of amount of both polymers on drug entrapment efficiency (DEE,%), bead size (µm) and cumulative drug release at 8 h (Q8h, %) were optimized using 3(2) factorial design. The DEE, average size and Q8h were found in the range of 65.08-91.02%, 976-1084 µm and 73.50-94.06% respectively. The beads were also characterized by FTIR, DSC, SEM and XRD. The experiential responses were coincided well with predicted values obtained by Design-Expert(®) 8.0.6.1 software. The swelling of beads were influenced by the pH of a release medium. The in vitro drug release from IPN beads exhibited sustained release Hixson-Crowell pattern with anomalous non-Fickian diffusion mechanism concluding that the developed sodium alginate-egg albumin IPN composite beads are suitable for sustained delivery of oxcarbazepine for desired period.

Locust bean gum in the development of sustained release mucoadhesive macromolecules of aceclofenac.

The study shows the development and optimization of locust bean gum (LBG)-alginate mucoadhesive macromolecules containing aceclofenac through ionotropic-gelation using 3(2) factorial design. The effect of amount of LBG and sodium alginate on drug entrapment efficiency (%DEE), % mucoadhesion at 8h (M8) and % in vitro drug release at 10h (%Q10h) were optimized. The percentage yield, average size and DEE of macromolecules were found within the range of 93.19 to 96.65%, 1.328 ± 0.11 to 1.428 ± 0.13 µm, and 56.37 to 68.54%, respectively. The macromolecules were also characterized by SEM, FTIR and DSC. The in vitro drug release from these macromolecules (84.95 ± 2.02 to 95.33 ± 1.56% at 10h) exhibited sustained release (first-order) pattern with super case-II transport mechanism. The swelling and mucoadhesivity of these macromolecules were affected by pH of the medium. The design established the role of derived polynomial equations and plots in predicting the values of dependent variables for the preparation and optimization.

Carrageenan: a natural seaweed polysaccharide and its applications.

Polysaccharides have been gaining interesting and valuable applications in the food and pharmaceutical fields. As they are derived from the natural source, they are easily available, non-toxic, cheap, biodegradable and biocompatible. Carrageenan is one among them, which fulfills the criteria of polysaccharide; it is a natural carbohydrate (polysaccharide) obtained from edible red seaweeds. The name Carrageenan is derived from the Chondrus crispus species of seaweed (Rhodophyceace) known as Carrageen Moss or Irish Moss, and Carraigin. A demand based on its application has been widely increasing in food and pharmaceutical sectors. Carrageenan has gained wide applications in experimental medicine, pharmaceutical formulations, cosmetics, and food industries. Through keen references of the reported literature on carrageenan, in this review, we have described about carrageenan, its properties, extraction and refining, and its food and pharmaceutical applications.

Lepidium sativum Linn.: a current addition to the family of mucilage and its applications.

Mucilage from the last decades has been found to be very attractive, interesting and useful in development of desired pharmaceutical dosage forms. Various applications of plant based mucilage have a wide potentiality in drug formulations. Lepidium sativum Linn. (family: Brassicaceae) is one of the mucilage containing fast growing, edible annual herb. Its various parts (roots, leaves and seeds) have been used to treat various human ailments. It mainly contains alkaloids, saponins, anthracene glycosides, carbohydrates, proteins, amino acids, flavanoids, and sterols as chief phytochemical constituents. Its seed extracts have been screened for various biological activities like hypotensive, anti-microbial, bronchodilator, hypoglycemic and allelopathic, whereas its seed coat mucilage has been isolated using different methods to make it effective excipient of desired functionality as a part of pharmaceutical applications. Through keen references of reported work on Lepidium sativum Linn., in this review, we have focused on its seed coat mucilage isolation methods, chemical constituents, pharmacological profile and versatile application of Lepidium sativum Linn.

Development of microencapsulation delivery system for long-term preservation of probiotics as biotherapeutics agent.

The administration of probiotic bacteria for health benefit has rapidly expanded in recent years, with a global market worth $32.6 billion predicted by 2014. The oral administration of most of the probiotics results in the lack of ability to survive in a high proportion of the harsh conditions of acidity and bile concentration commonly encountered in the gastrointestinal tract of humans. Providing probiotic living cells with a physical barrier against adverse environmental conditions is therefore an approach currently receiving considerable interest. Probiotic encapsulation technology has the potential to protect microorganisms and to deliver them into the gut. However, there are still many challenges to overcome with respect to the microencapsulation process and the conditions prevailing in the gut. This review focuses mainly on the methodological approach of probiotic encapsulation including biomaterials selection and choice of appropriate technology in detailed manner.

Galactomannan: a versatile biodegradable seed polysaccharide.

Polysaccharides have been finding, in the last decades, very interesting and useful applications in the biomedical and, specifically, in the biopharmaceutical field. Galactomannans are a group of storage polysaccharides from various plant seeds that reserve energy for germination in the endosperm. There are four major sources of seed galactomannans: locust bean (Ceratonia siliqua), guar (Cyamopsis tetragonoloba), tara (Caesalpinia spinosa Kuntze), and fenugreek (Trigonella foenum-graecum L.). Through keen references of reported literature on galactomannans, in this review, we have described occurrence of various galactomannans, its physicochemical properties, characterization, applications, and overview of some major galactomannans.

Pullulan: an exopolysaccharide and its various applications.

Pullulan is a non-ionic polysaccharide obtained from fermentation of black yeast like Aureobasidium pullulans and is currently exploited in food and pharmaceutical industries due to its unique characteristics. Due to its properties like non-toxic, non-immunogenic, non-carcinogenic, non-mutagenic, pullulan is being explored for various biomedical applications viz., gene delivery, targeted drug therapy, tissue engineering, wound healing, and also being used in diagnostic applications like, perfusion, receptor, and lymph node target specific imaging and vascular compartment imaging. The unique linkage of α (1→4) and α (1→6) in pullulan endows this polymer with distinctive physical traits, including adhesive property and the ability to form fibers. This review article presents an historical outline, overview of properties, production, derivatives of pullulan, its versatile applicability and recent advances of pullulan.

Locust bean gum: a versatile biopolymer.

Biopolymers or natural polymers are an attractive class of biodegradable polymers since they are derived from natural sources, easily available, relatively cheap and can be modified by suitable reagent. Locust bean gum is one of them that have a wide potentiality in drug formulations due to its extensive application as food additive and its recognized lack of toxicity. It can be tailored to suit its demands of applicants in both the pharmaceutical and biomedical areas. Locust bean gum has a wide application either in the field of novel drug delivery system as rate controlling excipients or in tissue engineering as scaffold formation. Through keen references of reported literature on locust bean gum, in this review, we have described critical aspects of locust bean gum, its manufacturing process, physicochemical properties and applications in various drug delivery systems.

An insight into the emerging exopolysaccharide gellan gum as a novel polymer.

The microbial exopolysaccharides are water-soluble polymers secreted by microorganisms during fermentation. The biopolymer gellan gum is a relatively recent addition to the family of microbial polysaccharides that is gaining much importance in food, pharmaceutical and chemical industries due to its novel properties. It is commercially produced by C.P. Kelco in Japan and the USA. This article presents a critical review of the available information on the gum synthesized by Sphingomonas paucimobilis with special emphasis on its fermentative production. Factors affecting the fermentative production of gellan gum and problems associated with mass transfer have been addressed. Classification and trade names of gellan gum has been specified. Characteristics of gellan gum with respect to its structure, physicochemical properties are discussed. An attempt has also been made to review the current and potential applications of gellan gum in food, pharmaceutical and other industries.

Raft forming system-an upcoming approach of gastroretentive drug delivery system.

In recent era various technologies have been made in research and development of controlled release oral drug delivery system to overcome various physiological difficulties such as variation in gastric retention and emptying time. To overcome this drawback and to maximize the oral absorption of various drugs, novel drug delivery systems have been developed. Gastroretentive drug delivery system is facing many challenges which can be overcome by upcoming newly emerging approach i.e. raft forming system. The purpose of writing this review is to focus on recent development of stomach specific floating drug delivery system to circumvent the difficulties associated with formulation design. Various gastroretentive approaches that have been developed till now are also discussed. The present study provides valuable information & highlights advances in this raft forming system. This review attempts to discuss various factors like physiological factors, physicochemical factors and formulation factors to be considered in the development of the raft forming system. Different types of smart polymers used for their formulation have also been summarized. The review focuses on the mechanism, formulation and development of the raft forming system. This review also summarizes the studies to evaluate the performance and application of these systems. The study finally highlights advantages, disadvantages, and marketed preparation of the raft forming system.

Pharmaceutical applications of various natural gums, mucilages and their modified forms.

A large number of plant based pharmaceutical excipients are available today. Gums and mucilages are the most commonly available plant ingredients with a wide range of applications in pharmaceutical and cosmetic industries. They are being used due to their abundance in nature, safety and economy. They have been extensively explored as pharmaceutical excipients. They are biocompatible, cheap and easily available. Natural materials have advantages over synthetic ones since they are chemically inert, nontoxic, less expensive, biodegradable and widely available. They can also be modified in different ways to obtain tailor-made materials for drug delivery systems and thus can compete with the available synthetic excipients. Recent trend toward the use of plant based and natural products demands the replacement of synthetic additives with natural ones. In this review, we describe the pharmaceutical applications of various natural gums, mucilages and their modified forms for the development of various drug delivery systems.

Development of modified release gliclazide biological macromolecules using natural biodegradable polymers.

Modified release biological macromolecules (beads) of gliclazide using sodium alginate combined with either gellan gum or pectin in different ratios were prepared by Ionotropic gelation method. Biological macromolecules were evaluated for different physico-chemical parameters. Increase in polymers proportion showed difficulty in production of biological macromolecules due to high viscosity of dispersion. As the polymer concentration increases, the swelling and entrapment efficiency of drug increased. Compared to all other batches and commercial modified release gliclazide tablet, formulated biological macromolecules of sodium alginate with pectin (2:1 ratio) and with gellan gum (6:0.75 ratio) exhibited spherical shape, biphasic in vitro release profile and initial high drug release followed by moderate release up to 12 h as matrix diffusion kinetics and Higuchi model as well as Korsmeyer model.

Evaluation of mucilage of Hibiscus rosasinensis Linn as rate controlling matrix for sustained release of diclofenac.

This article reports the exploitation of novel hydrophilic excipient, that is, mucilage from Hibiscus rosasinensis Linn, for the development of sustained release tablet. Swelling ratio and flow properties analyses of dried mucilage powder were carried out. A 3(2) full factorial design was used. In factorial design, amounts of dried mucilage and dibasic calcium phosphate (DCP) were taken as independent factors and percentage drug release in 60 and 300 min and time for 80% drug release as dependent variables. Matrix tablet containing dried mucilage and diclofenac sodium (DS) was prepared through direct compression techniques. DS tablets were evaluated for hardness, friability, weight variation, in vitro drug release and water uptake, and mass loss study. The dried mucilage powder shows superior swelling capacity and excellent flow properties. Prepared tablets have acceptable hardness, friability, and uniformity in weight. It was found that batch HD8 fulfills all selected criteria. Drug release kinetics from these formulations corresponded best to the zero-order kinetics. Water uptake was independent whereas mass loss was dependent on agitation speed. The concept of similarity factor (f(2)) was used to prove similarity of dissolution profile in distilled water and phosphate buffer and was found to be 90.68. It was concluded that mucilage can be used as release-retarding agent for 12 h when the drug-mucilage ratio was 1:1.5. So, matrix tablet containing dried mucilage is most suitable for sustained release of DS.

Spherical crystals of celecoxib to improve solubility, dissolution rate and micromeritic properties.

Celecoxib spherical agglomerates were prepared with polyvinylpyrrolidone (PVP) using acetone, water and chloroform as solvent, non-solvent and bridging liquid, respectively. The agglomerates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), IR spectroscopic studies and scanning electron microscopy (SEM). The IR spectroscopy and DSC results indicated the absence of any interactions between drug and additives. XRD studies showed a decrease in crystallinity in agglomerates. The crystals exhibited significantly improved micromeritic properties compared to pure drug. The loading efficiency (% or mg drug per 100 mg crystals) was in the range of 93.9 +/- 2.3 and 97.3 +/- 1.3% (n = 3) with all formulations. The aqueous solubility and dissolution rate of the drug from crystals was significantly (p < 0.05) increased (nearly two times). The solubility and in vitro drug release rates increased with an increase in PVP concentration (from 2.5 to 10%). The SEM studies showed that the crystal posseses a good spherical shape with smooth and regular surface.