Formulation Of Solid Dosage Forms Research Articles

Formulation and Evaluation of Conventional Metronidazole Tablets using Natural Gum Extracted from Grewia species

Aims: The pharmaceutical world has been paying increasing attention to the extraction, development and use of natural gums as binders in the formulation of solid dosage forms. The use of natural gums as binders is more advantageous than the use of synthetic ones due to availability, low cost, biodegradability and biocompatibility. In this study, gum extracted from Grewia species was compared with that fromAcacia in metronidazole tablets.
 Study Design: Ten batches of metronidazole tablets were formulated with varied concentration of Grewiaspp gum and Acacia gum.
 Place and Duration of Study: The study was carried out in Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Delta State University, Abraka, Nigeria; between January and December 2019.
 Methodology: Five batches of metronidazole tablets containing 0.5, 0.75, 1.0, 1.25 and 1.5% w/w of Grewia gum were preparedby wet granulation. Resulting granules were characterised by measuring flow and packing properties. In other experiments, five batches of tablets were formulated using same concentration of gum, with Acacia gum substituted for Grewia gum. Both sets of granules were compressed into tablets using tableting machine at a load of 27 arbitrary units. Tablets so formed were evaluated for hardness, friability, disintegration time, drug content and drug release profiles. Drug – excipient interaction was investigated with FTIR.
 Results: The resulting metronidazole tablets showed hardness of 5.46 kgF to 7.87 kgF (Grewiagum) and 6.06 kgF-8.20 kgF (Acacia gum). Friability percentages of all the batches were above 1% except for A3-A5 and B5 which are less than 1%. All formulations released more than 75 % of the drug content within 60 min. The FTIR analysis revealed no interaction between the metronidazole and Grewia species gum.
 Conclusion: Metronidazole granules and tablets were successfully prepared using Grewiagum and showed comparable pre-compression and post-compression properties with those formulated with Acacia.

Solubility Enhancement of Lipophilic Drugs-Solid Self Micro-Emulsifying Drug Delivery System

Approximately more than 50%of new chemical entities exhibit poor aqueous solubility and present a major challenge to modern drug delivery system, because of their low bioavailability. The bioavailability of these drugs (BCS class II) is rate-limited by its dissolution, so that even a small increase in dissolution rate sometimes results in a large increase in bioavailability. The rate and extent of absorption of class II compounds is highly dependent on the performance of the formulated product. Self-microemulsifying drug delivery systems (SMEDDS) are usually used to improve the bioavailability of hydrophobic drugs. Conventional SMEDDS, however, are mostly prepared in a liquid form, which can produce some disadvantages. Accordingly, solid SMEDDS (S-SMEDDS), prepared by solidification of liquid/semisolid self-emulsifying (SE) ingredients into powders, have gained popularity. This article presents an account on types of self-emulsifying formulations with emphasis on formulation of solid dosage forms, characterization and in-vitro analysis.

Self microemulsefying and non-self microemulsefying liquisolid tablet of felodipine

Liquisolid formulation involves dissolution or dispersion of the drug in a liquid before formulation of solid dosage form using solid adsorbent as a carrier. The liquid component usually utilizes simple solvent system. Self emulsifying liquids can provide another alternative liquid for enhanced dissolution. The objective of this work was to develop and evaluate non-self emulsifying and self emulsifying liquisolid tablet for enhanced dissolution rate of felodipine. The former utilized polyethylene glycol 400 which was the best solvent and the later employed a mixture of castor oil with labrasol and transcutol as self emulsifying system. A mixture of avicel PH 102 and aerosil 200 was used as solid adsorbent with croscarmellose being used as superdisintegrent. Formulation of the drug as liquisolid tablets enhanced the dissolution rate compared with the standard tablet prepared using the unprocessed drug powder with the same tablet excipients. The self emulsifying tablet showed faster release pattern compared with the non-self emulsifying tablet. The thermal analysis studies indicated the presence of the drug in a solution form in the tablet formulations. In conclusion liquisolid tablet formulation can enhance the dissolution rate of felodipine with self emulsifying liquid system being more efficient.

Micro- and macrostructural characterization of polyvinylpirrolidone rotary-spun fibers

The application of high-speed rotary spinning can offer a useful mean for either preparation of fibrous intermediate for conventional dosage forms or drug delivery systems. Polyvinylpyrrolidone (PVP) and poly(vinylpyrrolidone-vinylacetate) (PVP VA) micro- and nanofibers of different polymer concentrations and solvent ratios were prepared with a high-speed rotary spinning technique. In order to study the influence of parameters that enable successful fiber production from polymeric viscous solutions, a complex micro- and macrostructural screening method was implemented. The obtained fiber mats were subjected to detailed morphological analysis using scanning electron microscope (SEM), and rheological measurements while the microstructural changes of fiber samples, based on the free volume changes, was analyzed by positron annihilation lifetime spectroscopy (PALS) and compared with their mechanical characteristics. The plasticizing effect of water tracked by ortho-positronium lifetime changes in relation to the mechanical properties of fibers. A concentration range of polyvinylpyrrolidone solutions was defined for the preparation of fibers of optimum fiber morphology and mechanical properties. The method enabled fiber formulation of advantageous functionality-related properties for further formulation of solid dosage forms.

Mechanism-based prediction of particle size-dependent dissolution and absorption: Cilostazol pharmacokinetics in dogs

A previously developed physiologically based pharmacokinetic (PBPK) model for gastro-intestinal transit and absorption was combined with a mechanistic dissolution model of the Noyes–Whitney type for spherical particles with a predefined particle size distribution. To validate the combined model, the plasma concentration–time curves for cilostazol obtained in beagle dogs using three different types of suspensions with varying particle diameters were simulated. In vitro dissolution information was also available for different formulations, but this data could only predict the in vivo outcome qualitatively. The mechanistic PBPK model, on the other hand, could predict the influence of the particle size on the rate and extent of absorption under both fasted and fed conditions accurately, and the gap between the in vitro dissolution data and the in vivo outcome could successfully be explained. We conclude that by integrating the processes of particle dissolution, gastro-intestinal transit and permeation across the intestinal epithelium into a mechanistic model, oral drug absorption from suspensions can be predicted quantitatively. The model can be applied readily to typical formulation development data packages to better understand the relative importance of dissolution and permeability and pave the way for successful formulation of solid dosage forms.

Cefuroxime axetil solid dispersions prepared using solution enhanced dispersion by supercritical fluids

Cefuroxime axetil (CA) solid dispersions with HPMC 2910/PVP K-30 were prepared using solution enhanced dispersion by supercritical fluids (SEDS) in an effort to increase the dissolution rate of poorly water-soluble drugs. Their physicochemical properties in solid state were characterized by differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectrometry (FT-IR) and scanning electron microscopy. No endothermic and characteristic diffraction peaks corresponding to CA were observed for the solid dispersions in DSC and PXRD. FTIR analysis demonstrated the presence of intermolecular hydrogen bonds between CA and HPMC 2910/PVP K-30 in solid dispersions, resulting in the formation of amorphous or non-crystalline CA. Dissolution studies indicated that the dissolution rates were remarkably increased in solid dispersions compared with those in the physical mixture and drug alone. In conclusion, an amorphous or non-crystalline CA solid dispersion prepared using SEDS could be very useful for the formulation of solid dosage forms.

Application of clay as a means of support to biomaterial with anti-inflammatory agents

In the last fifteen years, there have been significant changes in the production of medicines, mainly in the addition of new components to the formulation of solid dosage forms. The current trend of “back to nature” to lead to a healthier life has led those who are engaged in the pharmaceutical field to develop new formulations that allow the use of natural products of plant originFor example, excipient ingredients, used as carriers for a drug's active ingredients, are now being used. These are incorporated into a drug in order to facilitate the drug's preparation, maintenance, or administration. The excipient is beneficial to the patient because it allows the drug to be easily administered and absorbed by the human body [3]There is evidence that the clays have great potential for both absorption and adsorption due to its tiny particles. In addition, it has been reported that some clays have an effective antiseptic and healing ability [5–8]In the present work, a clay called bentonite was tested as a support vehicle of an inflammatory agent derived from a Mexican native plant called Distictis buccinatoria, commonly named “Tonacaxóchitl”. Studies carried out by Rojas et al. have shown that the organic extract of this plant has important antibacterial, antifungal, cytotoxic and anti-inflammatory properties [9]

Comparative study of pharmaceutical properties of some new derivatives of sulfamethoxazole

This paper reports the changes in various physical properties associated with the derivatization of sulfamethoxazole. The properties studied include moisture content, crystallanity, particle size distribution, porosity, flow, compressibility and compactability. It was found that the derivatives, salicylidene-sulfamethoxazole-Zn(II) • H2O and salicylidene-sulfamethoxazole-Cu(II) • H2O are crystalline substances. The moisture content was found to be highest in salicylidene-sulfamethoxazole-Zn(II) • H2O followed by salicylidene-sulfamethoxazole-Cu(II) • H2O and sulfamethoxazole. The copper complex contained only chemically bonded water, whereas the zinc complex contained both bonded and absorbed water, which affected the strength of the tablets prepared from the three materials accordingly. The particle size decreased on derivatization and complexation with metal ions and the trend was: sulfamethoxazole > salicylidene-sulfamethoxazole-Cu(II) • H2O > salicylidene-sulfamethoxazole-Zn(II) • H2O. This trend was represented by better compactability shown by salicylidene-sulfamethoxazole-Cu(II) • H2O and salicylidene-sulfamethoxazole-Zn(II) • H2O as compared with sulfamethoxazole. Salicylidene-sulfamethoxazole-Zn(II) • H2O had the highest porosity followed by salicylidene-sulfamethoxazole-Cu(II) • H2O, and sulfamethoxazole; this resulted in better compressibility behavior of the complexes. Thus it was observed that salicylidene-sulfamethoxazole-Cu(II) • H2O and salicylidene-sulfamethoxazole-Zn(II) • H2O formed stronger compacts. The values of angle of repose and flow rate show better flow properties for salicylidene-sulfamethoxazole-Cu(II) • H2O as compared with sulfamethoxazole and salicylidene-sulfamethoxazole-Zn(II) • H2O. It was concluded that derivatization substantially changed the pharmaceutical properties, which have important role to play in formulation of solid dosage form.

Application of instrumental evaluation of color for the pre-formulation and formulation of rabeprazole

The aims of this study were to fast screen the compatibility of rabeprazole and excipients using a spectrocolorimeter and to examine the relationship between the color change value and drug contents/drug degradation products in solid dosage forms. The color change values of rabeprazole-excipient mixtures were measured using a spectrocolorimeter, with six tablet formulations compressed using a single-punch instrumental tablet press. The rabeprazole and degradation products contents in the tablets were analyzed using an HPLC method, with the color change values of the tablets measured using spectrocolorimetery for 4 weeks. These experiments indicated that the instrumental evaluation of color was a speedy, simple and useful tool in the determination of the interaction between the drug and excipients, as well as in the formulation of solid dosage forms. The relationships of the % reduced drug contents versus the color change value, and those of the % drug degradation products versus the color change value were exponentially increased in formulations containing zinc stearate. On stress testing, the color change value of rabeprazole was inconsistent with previous reports, as the degradation of rabeprazole can be greatly influenced by humidity as well as temperature. Consequently, these results highlight the potential of color formation in the application of pre-formulation and formulation of drugs.

Preparation of microcapsules with self-microemulsifying core by a vibrating nozzle method

Incorporation of drugs in self-microemulsifying systems (SMES) offers several advantages for their delivery, the main one being faster drug dissolution and absorption. Formulation of SMES in solid dosage forms can be difficult and, to date, most SMES are applied in liquid dosage form or soft gelatin capsules. This study has explored the incorporation of SMES in microcapsules, which could then be used for formulation of solid dosage forms. An Inotech IE-50 R encapsulator equipped with a concentric nozzle was used to produce alginate microcapsules with a self-microemulsifying core. Retention of the core phase was improved by optimization of encapsulator parameters and modification of the shell forming phase and hardening solution. The mean encapsulation efficiency of final batches was more than 87%, which resulted in 0.07% drug loading. It was demonstrated that production of microcapsules with a self-microemulsifying core is possible and that the process is stable and reproducible.

Porous cellulose matrices — a novel excipient for the formulation of solid dosage forms

A novel pharmaceutical aid prepared from a specially processed cellulose is presented. The material, which consists of highly porous spherical cellulose beads, is regarded as having a considerable field of application in dry pharmaceutical formulation. Primarily, the material may act as a multiple unit carrier and release controlling system as well as an additive for the compression of multiple unit preparations in the form of compressed and disintegrating tablets. This paper describes formulation possibilities, and presents some of the essential characteristics and preliminary results on some applications.

Matrix forming capabilities of three calcium diluents

AbstractThe formulation of drug substances with excipients capable of forming a matrix structure is an approach which has been successfully applied to sustain medicament release following oral administration. Investigations of materials which possess matrix forming properties have been limited to a few polymeric substances such as polyvinyl chloride, polyethylene, acrylic copolymers, and cellulose derivatives 1-5 Calcium sulfate dihydrate, dibasic calcium phosphate dihydrate, and tribasic calcium phosphate have previously been used as fillers/diluents in the formulation of solid dosage forms. All three diluents exhibit poor solubility in media of pH 1.1 and are practically insoluble in media of pH 4.0 to 7.5. In addition, when blended with one of three drug candidates and compressed these materials sustain drug release via a matrix diffusional process at higher pH corresponding to that of the human intestine. These findings led to an investigation of these calcium diluents as matrix forming agents in sust...

Dissolution Characteristics of Interactive Powder Mixtures. Part Two: Effect of Surface Characteristics of Excipients

AbstractThe efficiency of interactive powder mixtures as a process used to increase the dissolution rate of poorly soluble drugs is dependent on the degree and extent of dispersion of drug agglomerates into individual particles. Furthermore, the dispersion mechanism is dependent on the surface characteristics of excipient particles.The smooth excipient particles produce interactive powder mixture with high dissolution efficiency for poorly soluble drugs. In contrast, when the excipient particulate surfaces have high rugosity, the corresponding interactive powder mixtures produce lower dissolution efficiency. The main reason is the entrapment of drug particles and agglomerates into the indentations already present on excipient particulate surfaces. When the entrapment sites are blocked with fine excipient particles the dissolution efficiency increases significantly. Therefore, surface characteristics of excipient particles should be examined carefully before formulation of solid dosage forms using interact...