Spherical Crystallization: A Novel Drug Delivery Approach (original) (raw)
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Spherical crystallization is a particle design technique, by which crystallization and agglomeration can be carried out simultaneously in one step and which has been successfully utilized for improvement of flowability, compactability and bio-availability of crystalline drugs. General methods of spherical crystallization are spherical agglomeration, emulsion solvent diffusion and ammonia diffusion method. The principle steps involved in the process of spherical crystallization are flocculation zone, zero growth zone, fast growth zone and constant size zone. Spherical crystallization is having wide applications in pharmaceuticals like improvement of flowability and compressibility of poorly compressible drugs, masking bitter taste of drugs and improving the solubility and dissolution rate of poorly soluble drug.
Spherical crystallization -A novel drug delivery system
INTERNATIONAL JOURNAL OF PHARMACY & LIFE SCIENCES , 2011
Today, the tablet is the most popular dosage form, covering around 50% of total oral drug delivery system and accounting 75% of all pharmaceutical preparation produced .It promotes statbility, portability and acceptable patient compliance .The quality of solid dosage form is primarily influenced by micromeritic characteristics such as the shape and size of drug crystal, especially in the case of poorly soluble drugs. To improve the dissolution rate of poorly soluble drugs, fine crystals are referred and this micronisation can change drug powder properties such as wettability, compressibility, packability and flow. Further, it is more beneficial to convert micro crystalline drugs into an agglomerated form using spherical crystallization technique. The resulting spherically agglomerated crystals can be directly prepared into a tablet, thus direct tabletting saves time and reduces cost .General methods of spherical crystallization are spherical agglomeration, emulsion, solvent diffusion method, ammonia diffusion method, neutralization method .The principle steps involved in the process of sc are flocculation zone, zero growth zone, fast growth zone, constant size zone .There is a wide application of spherical crystallization:-improvement of flow ability, compressibility of poorly compressible drug, masking bitter taste of drug, improving solubility and dissolution rate of poorly soluble drug and thus improve bioavailability of drug.
2017
Tablets have been choice of manufacturers over the years due to their comparatively low cost of manufacturing, packaging, shipping, and ease of administration; also have better stability and can be considered virtually tamper proof. A major challenge in formulation development of the tablets extends from lower solubility of the active agent to the elaborated manufacturing procedures for obtaining a compressible granular material. Moreover, the validation and documentation increases, as the numbers of steps increases for an industrially acceptable granulation process. Spherical crystallization (SC) is a promising technique, which encompass the crystallization, agglomeration, and spheronization phenomenon in a single step. Initially, two methods, spherical agglomeration, and emulsion solvent diffusion, were suggested to get a desired result. Later on, the introduction of modified methods such as crystallo‑co‑agglomeration, ammonia diffusion system, and neutralization techniques overcame the limitations of the older techniques. Under controlled conditions such as solvent composition, mixing rate and temperature, spherical dense agglomerates cluster from particles. Application of the SC technique includes production of compacted spherical particles of drug having improved uniformity in shape and size of particles, good bulk density, better flow properties as well as better solubility so SC when used on commercial scale will bring down the production costs of pharmaceutical tablet and will increase revenue for the pharmaceutical industries in the competitive market. This review summarizes the technologies available for SC and also suggests the parameters for evaluation of a viable product.
Spherical crystallization of drugs
Acta Pharmaceutica, 2000
Spherical crystallization of drugs Spherical crystallization of drugs is the process of obtaining larger particles by agglomeration during crystallization. The most common techniques used to obtain such particles are spherical agglomeration and quasi-emulsion solvent diffusion. Ammonia diffusion systems and crystallo-co-agglomeration are extensions of these techniques. By controlling process parameters during crystallization, such as temperature, stirring rate, type and amount of solvents, or excipient selection, it is possible to control the formation of agglomerates and obtain spherical particles of the desired size, porosity, or hardness. Researchers have reported that the particles produced have improved micromeritic, physical, and mechanical properties, which make them suitable for direct compression. In some cases, when additional excipients are incorporated during spherical crystallization, biopharmaceutical parameters including the bioavailability of drugs can also be tailored.
Crystal growth of drug materials by spherical crystallization
2002
One of the crystal growth processes is the production of crystal agglomerates by spherical crystallization. Agglomerates of drug materials were developed by means of non-typical (magnesium aspartate) and typical (acetylsalicylic acid) spherical crystallization techniques. The growth of particle size and the spherical form of the agglomerates resulted in formation of products with good bulk density, flow, compactibility and cohesivity properties. The crystal agglomerates were developed for direct capsule-filling and tablet-making. r
2012
Direct compression of powders is simplest and easiest way of making tablets. Good flowability and compressibility plays a major role for direct compression of drugs. There are several techniques available to impart desired compressibility to drugs. Spherical crystallization techniques are reliable techniques in which the drug crystals are modified using different solvents to directly compressible spherical agglomerates, which less economical and time saving. The use of spherical crystallization as a technique appears to be efficient alternative for obtaining suitable particles for direct compression. Spherical crystallization is a particle design technique, by which crystallization, agglomeration and spheronization can be carried out simultaneously in one step.
Spherical Crystallization in Solubility Enhancement
2018
Sachin Kumar Patil, Amulyaratna Behera, Shital Kumar Patil and Sunit Kumar Sahoo Department of Pharmaceutics, Ashokrao Mane College of Pharmacy, PethVadagaon, Dist. Kolhapur, Maharashtra, India. Department of Pharmaceutics, Vaagdevi Institute of Pharmaceutical Sciences, Bollikunta, Warangal, Andhra Pradesh, India. Department of Pharmaceutics, University Department of Pharmaceutical Sciences, Utkal University, Vani Vihar, Bhubaneswar, Odisha, India.
Powder Technology, 2018
Cycloserine, a high dose anti-tuberculosis agent, possesses poor flow properties and compression behaviour. The present study was aimed at improving the flowability, packing properties and compressibility of Cycloserine by spherical crystallization. Cycloserine was dissolved in a water and crystallised by pouring into anti-solvent, 1-Butanol, in presence of ethyl acetate which acts as a bridging liquid for formation of agglomeration. Further, spherical agglomeration process for Cycloserine was statistically optimised using the central composite design, keeping the 'rate of stirring' and 'amount of bridging liquid' as an independent factors and average particle size as the response. Optimised batch of Cycloserine spherical agglomerates (Cyc-SA) was further evaluated for sieve analysis, solid state characterisation studies and compaction behaviour (Kawakita analysis and Heckel study). The uniform spherical agglomerates were revealed in microphotographs of scanning electron microscopy while no chemical alteration in the Cycloserine was indicated by X-Ray powder diffraction, differential scanning calorimetry and Fourier-transform infrared spectroscopy during the crystallization. The excellent flow properties of Cyc-SA were demonstrated by Carr's index, Hausner ratio and Kawakita parameters as compare to plain drug. The enhanced particle size and uniform distribution of agglomerates have also contributed to improve flow properties of Cycloserine. Similarly, Heckel parameters like mean yield pressure and yield strength displayed superior compressibility of Cyc-SA. Thus, spherical crystallisation would be interesting technique for improving processability of high dose drug like Cycloserine.
FORMULATION AND EVALUATION OF SPHERICAL CRYSTAL AGGLOMERATES OF NISOLDIPINE
Utilization of herbs for medicinal purpose started in the early history of mankind several thousand years The aim of the present study was to prepare and characterize the spherical crystal agglomerates ofnisoldipine with different polymers like PEG 4000, PEG 6000, PVP and PVP K30 byusing Quassi emulsification solvent diffusion technique for enhancement of solubility, flowability, packability of nisoldipine.All the prepared agglomerates were evaluated for their flow behaviour, packability and solubility. The prepared spherical crystal agglomerates exhibited excellent physicochemical properties like solubility, flowability, packability compared with the pure nisoldipine. Agglomerates AG15 showed the better solubility and drug release in comparison of pure drug. The agglomerates AG15 was further characterized by using SEM, X-Ray diffractometry and differential scanning calorimetry. SEM studies showed that the crystal possesses a good spherical shape with smooth and regular surface.DSC thermo grams showed the changes in the melting peak of the nisoldipine in spherical crystal agglomerates suggesting the change in crystallinity of nisoldipine.The XRD revealed a characteristic decrease in the crystallinity of the nisoldipine.These results show that partial amorphization of drug leads to enhancement of drug solubility and dissolution rate.
Preparation of Spherical Crystal Agglomerates via Crystallo-Co-Agglomeration Technique
2012
The purpose of this research was to obtain directly compressible agglomerates of aceclofenac-paracetamol containing desired ratio of drugs using a crystallo-coagglomeration technique. Crystallo-co-agglomeration is an extension of the spherical crystallization technique, which enables simultaneous crystallization and agglomeration of 2 or more drugs or excipients. Acetone-water system containing PEG 6000, PVA and HPMC K100M was used in crystallization system. Acetone acted as a good solvent for Aceclofenac and bridging liquid for agglomeration. Aceclofenac was crystallized from acetone and agglomerated with Paracetamol. The agglomerates were evaluated for micromeritic properties, mechanical properties, moisture content, compressibility, packability and in vitro dissolution study. The compatibility study was done by DSC, XRPD, FTIR and surface morphology was done by SEM. The spherical agglomerates contained an aceclofenac-paracetamol ratio in the range of 0.20 to 0.201. The result rev...