SOLID DISPERSION EXTENDED-RELEASE SYSTEM: A REVIEW

SOLID DISPERSION EXTENDED-RELEASE SYSTEM: A REVIEW

Kishore Kumar Puhan *, Suburayalu Raja and N. K. Choudhary

Department of Pharmacy, B. R. Nahata College of Pharmacy, Mandsaur University, Rewas Dewda Road, SH - 31, Mandsaur, Madhya Pradesh, India.

ABSTRACT: Solid dispersion extended-release system involves amorphization of drug material that leads to creating an alternative pathway for poorly water-soluble drugs. The drug increases solubility due to an increase in apparent solubility of the particular drug. Crystalline lattices of the drug are disturbed during its manufacture, which minimizes the crystal packing energy for solubilization. Along with this, molecular level dispersion with the carrier increases the dissolution rate. Different challenges are involved in this type of system. Supersaturation creates the separation of solute and solution, causing it to be thermodynamically unstable. Recrystallization due thermodynamically unstable state of the system causes Intramatrix recrystallization. Agglomeration, polymer hydration and clumping of the system lead to the prevention of dissolution of non-ionic, amorphous active drugs. Various manufacturing processes such as mechanical stress, downstream processing, etc., significantly impact the performance of the drug systems. Despite these issues, approaches for SDS have been used to overcome these challenges. They are based on hydrophilic polymers, hydrophobic polymers, wax, and lipids systems. At present, the perfect SDS isn’t readily available, but with precision and proper formulation, reprecipitation of SDS can be avoided, which can improve bioavailability issues in society.

Keywords: Solid Dispersion, Supersaturation, recrystallization, apparent solubility,  hydrophobic, hydrophilic, Extend release

INTRODUCTION: Medication advancement pipelines actually incorporate a high extent of medications that have poor fluid dissolvability. It has been accounted for that up to 40% of the medications presently on the lookout, and up to 70% of investigational drugs show poor watery solvency ¹. This poor watery dissolvability presents a test since disintegration in the gastrointestinal climate is essential for fundamental assimilation and medication viability.

Throughout the most recent couple of many years, numerous dissolvability empowering plans have been researched and created to defeat this issue, including the utilization of salts ², co-crystals ³, self-emulsifying drug conveyance frameworks and cosolvents ⁴, cyclodextrins ⁵, nanoparticles ⁶ and strong scatterings framework (SDS) ^{7, 8} .

Among these procedures, SDS, where the medication is amorphized, has acquired expanding consideration because of their high evident medication solvency in contrast with the medication's harmony glasslike dissolvability ⁹. Besides, it has been shown that this expanded clear dissolvability might be accomplished without influencing layer penetrability ¹⁰. Solvency and porousness are the two principal factors that oversee drug ingestion ¹¹.

Along these lines, the evident solvency of SDS is a huge benefit over different strategies since different procedures can't increment clear dissolvability without a corresponding abatement in penetrability (e.g., cosolvents, cyclodextrins, surfactants) ¹⁰. SDS is made utilizing various methodologies, yet the most widely recognized methodology is the dissolvable dissipation, for example, splash drying ¹², or warm preparing, for example, hot-liquefy expulsion ¹³.

The vast majority of the examination on SDS answered to date has zeroed in on (a) quick delivery, (b) supersaturation and precipitation hindrance, or (c) the anticipation of recrystallization during capacity ¹⁴. Notwithstanding, for in-adequately water-solvent medications that have a short half-life, Extended-Release SDS might be of interest by limiting the organization's recurrence.

A low organization recurrence is alluring for drugs that show focus subordinate poisonousness. It has additionally been shown that diminishing the pace of supersaturation lessens the inclination toward recrystallization, so the disintegration profile might be advanced by changing the delivery rate ¹⁵.

MARKETED SOLID DISPERSION EXTENDED-RELEASE SYSTEM

Approaches for Solid dispersion Extend release system and its Mechanism: Appropriately, this survey gives a logical conversation on Solid scattering and their medication discharge instruments which are significant for understanding the particular difficulties of joining strong scattered medication in Extended-discharge measurements structures.

Solubility Advantage and the Stability of Solid Dispersion System: Solubility advantage and the soundness of SDS The accompanying condition portrays watery thermodynamic solubility ²³: S=f(Crystal Packing Energy +Cavitation Energy + Solvation Energy). In this condition, the gem pressing energy is the energy important to upset the gem grid and eliminate the disengaged particles (endothermic). The cavitation energy represents the energy important to disturb the water and make cavities that go about as a host for the medication particle (endothermic). Finally, the solvation energy is the ideal energy that outcomes from cooperations between the dissolvable and the solute particles (exothermic), .subsequently limiting the precious stone pressing energy needed for solubilization. The gem pressing energy is the most elevated regarding enthalpy, so it is the main thrust behind the solubilization interaction. This could clarify the critical upgrades in clear dissolvability commonly saw in strong scatterings frameworks. Medications inside an SDS contain put away potential energy that is delivered on contact with the disintegration media to constrain the medication into a supersaturated express that surpasses the harmony solvency ⁹. This supersaturated state is thermodynamically temperamental, so the solute and arrangement will, in general separate and elevate drug recrystallization to diminish the free energy in the framework. To keep a high-supersaturation state and amplify drug assimilation, drug excipients like polymers are utilized to restrain stage partition, nucleation, and precious stone development. This wonder is alluded to as the parachute impact ⁹.

Notwithstanding the thermodynamic dissolvability advantage in SDS, the medication is likewise normally scattered at the atomic level inside the transporter, in this manner expanding the surface territory and the disintegration rate, as per the Noyes–Whitney condition ²⁴. The enactment energy for nucleation is represented by the level of supersaturation and the degree of interfacial pressure. If the initiation energy is defeated during disintegration, drug recrystallization happens ²⁵. Thus, until a basic level of supersaturation (Cmin) is reached, no nucleation will happen (in any event during a specific time span), and the framework will stay in a metastable state. Nucleation and gem development lead to diminished focus, which ultimately dips under Cmin in stage III. At this stage, no new cores are framed; however gem development proceeds, further lessening the focus to the harmony fixation (Cs).

In this manner, apparently keeping up the disintegration rate with the goal that supersaturation stays beneath the basic supersaturation Cmin will forestall nucleation and development, subsequently augmenting ingestion. This can be a motivating force to figure Extended-discharge SDS, specifically for intensifies that show quick recrystallization in their supersaturated state. This was affirmed utilizing bi-phasic disintegration study conditions comprising of a fluid stage and an upper natural stage; higher dividing into the natural stage was accomplished with polymers showing the lower degree of supersaturation ²⁷. This was ascribed to their capacity to stay beneath the basic nucleation edge and consequently to limit nucleation and development. The advantages would be less apparent for drugs that recrystallize gradually, on the grounds that these mixtures typically display fluid stage detachment and generally exist together at high shapeless dissolvability ¹⁴. The dissolvability benefit of SDS can likewise be kept up by adding a polymer or other drug excipient to restrain nucleation and precious stone development. The presence of polymers or thickness upgrading specialists adjusts the gem development measure both in arrangement and by adsorption onto the gem ^{25, 28}.

Solid-State Physical Stability of Drugs in SDS: Past the difficulties in regards to sedate crystallization in arrangement, there is the worry that an undefined medication may recrystallize during capacity. Because of the great degree of free energy comparative with translucent medications, nebulous medications tend to recrystallize into a glass like structure that is all the more thermodynamically steady. Such a wonder would almost certainly discredit any dissolvability advantage given by a SDS and result in diminished bioavailability.  Subsequently, transporters, for example, polymers should likewise add to the assembling of truly stable SDS. The hindrance of crystallization from polymers can be credited to various systems, like enemy of plasticization, diminished atomic portability ²⁹, expanded actuation energy ²⁵, or drug–polymer collaborations through van der Walls associations and hydrogen holding ³⁰. The presence of water influences the dependability of SDS, since water ingestion causes plasticization and a resulting decline in the glass change temperature (Tg) ³¹.

A lower Tg prompts expanded sub-atomic portability, which favors crystallization ³². SDS are commonly more delicate to dampness on the grounds that shapeless medications are generally more hygroscopic than their translucent partners. Temperature is another factor that favors nucleation by advancing atomic versatility ³¹. Broadened discharge SDS are, by definition, presented to disintegration media for delayed timeframes, so they show recrystallization inside or on the outside of the measurement structure.

This can be kept away from, or if nothing else deferred, by various detailing approaches that will be examined beneath.

Mechanisms for Extended-Release of SDS: Broadened drug discharge is a mind-boggling wonder that includes various components reliant on medication and polymer properties at some random time during the disintegration cycle. While the components for the all-inclusive arrival of solvent medications have been generally depicted ³³, scarcely any investigations portray the all-encompassing arrival of SDS and their capacity to create supersaturation. Supersaturating frameworks have explicit properties, and difficulties (e.g., expanded evident dissolvability, metastable state); however, past information on broadened discharge instruments should be thought of on the grounds that these delivery systems additionally apply to broadened discharge SDS. Appropriately, drug discharge systems can be portrayed by dispersion (in the long run connected with growing and additionally disintegration) or by corruption and disintegration.

Medication discharge by dissemination can happen from both hydrophilic and hydrophobic lattices ³³. Medication and polymer disintegration may likewise add to the medication discharge component, contingent upon their separate solvency in the disintegration media. In hydrophilic frameworks, the medication is disintegrated in the transporter or suspended as a total before dissemination through the grid material or coagulated organization. Contingent upon the properties of the polymer, growing and polymer disintegration can either increment or decline the delivery rate. At the point when a polymer grows, the length of the dispersion pathways builds, along these lines diminishing the focus inclination and the main impetus for dissemination. Then again, polymer expanding likewise brings about an expanded versatility of polymer macromolecules (because of polymer unwinding) and drug particles, which can prompt expanded delivery rates.

Contingent upon the prevailing system, drug delivery will be expanded or diminished. Medication discharge from solid frameworks in which a medication is scattered inside a polymer transporter has been recently portrayed and numerically displayed for translucent medications utilizing Fick's law of dissemination ¹⁷. Since this instrument includes solubilizing the medication inside the measurement structure, the significant trouble for these definitions is to forestall recrystallization and to deliver the medication proficiently ³⁴. Hydrophobic polymers that don't corrupt or disintegrate in fluid media (or do so just to a little degree), discharge the medication by means of watery pores or through dissemination through the polymer transporter after the medication comes into contact with the disintegration medium ²¹. The medication discharge measure makes a permeable organization that further works with disintegration. This instrument appears to be more pertinent to drugs that display satisfactory solvency because a permeable organization should be framed during drug disintegration.

Medication discharge via transporter disintegration and debasement seems, by all accounts, to be a promising methodology for the all-encompassing arrival of SDS since this component doesn't need water take-up; along these lines, it is probably going to dispose of recrystallization issues ³⁵. While disintegration alludes to a deficiency of some piece of the polymer mass or the polymer spine, polymer debasement alludes to chain scissions in which chains are cut into oligomers and monomers ³⁶. Upon contact with the disintegration media, disintegration can happen on a superficial level in particular or inside the measurement structure, contingent upon the properties of the polymer.

Challenges of Extended-Release Solid Dispersions System:

• Intra matrix recrystallization
• Polymer and amorphous drug gelling
• Impact of the manufacturing process and downstream processing

Intramatrix Recrystallization: The thermo-dynamically shaky territory of SDS may prompt recrystallization because of tablet hydration during disintegration. This is dangerous on the grounds that recrystallization will probably discredit the advantageous impacts of the expanded evident medication dissolvability given by the shapeless structure.

Excipients like hydrophilic polymers, which take into account the infiltration of the disintegration medium, are especially dependent upon this wonder. For instance, an SDS of carvedilol in polyvinylpyrrolidone (PVP) neglected to observably improve the disintegration profile since recrystallization happened during disintegration and underlying unwinding ³⁷.

It is conjectured that water is consumed by the tablet, which brings about a glass to elastic change. This change builds the atomic portability of the medication inside the dose structure, and this can prompt recrystallization ³⁴. On the other hand, the thickness of a gel layer upsets nucleation and development by forestalling sub-atomic revamp and sub-atomic connections ^{22, 28}. The main thrust behind the recrystallization of a medication relies principally upon the medication's physicochemical properties and, in this manner differs starting with one medication then onto the next ⁹.

Scientists have utilized X-beam diffraction to identify the recrystallization of beta-carotene in the gel layer of compacted tablets dependent on hydroxypropyl methylcellulose (HPMC) during their disintegration ³⁸. In any case, dissimilar to these HPMC-based tablets, no recrystallization of beta-carotene was seen during the disintegration of tablets dependent on hydroxypropyl methyl-cellulose acetic acid derivation succinate (HPMC-AS).

HPMC-AS is an acidic cellulosic polymer that contains both hydrophilic and hydrophobic locales, and it ionizes and solubilizes in the arrangement at pH 5.5 or more ¹². The capacity of HPMC-AS to keep up the medication in its nebulous state was credited to the exceptionally lethargic tablet lattice hydration, which brings about a lofty fixation slope and a short dispersion way through the tablet into the disintegration medium. Specialists presumed that the beginning of recrystallization was subject to the hydration energy of the lattice ³⁸. This was affirmed by another investigation of an SDS of carbamazepine, in which hydrophobic waxes were utilized as a hydrophobic excipient to lessen the entrance of the disintegration medium and accordingly defer or forestall the recrystallization of carbamazepine in the tablets ³⁴. The in-corporation of glyceryl behenate (Compritol® C888) as a delivery modifier expanded the hydro-phobicity of PVP-based SDS to such an extent that the medication and polymer were broken up at a comparative rate as water ingressed, in this way deferring or forestalling recrystallization. Without glyceryl behenate, carbamazepine recrystallized even beneath the immersion solvency because of a microenvironmental focus that surpassed drug dissolvability ³⁴. The hydrophobicity and surface territory to-volume proportion of these measurements structures were demonstrated to be the essential factors that forestalled recrystallization and controlled medication discharge.

Polymer and Amorphous Drug Gelling: Polymer hydration and gelling can advance recrystallization just as ruin drug discharge. Gelling, bunching, and agglomeration were seen during the disintegration of PVP-covered SDS dabs and these cycles forestalled the total disintegration of a nonionic, shapeless API ³⁹. In the wake of gelling, the medication should diffuse through the gel layer to be delivered. Hence, the disintegration happens all the more gradually and is inadequate. Actually, dots made with Eudragit® L100 (poly (methacrylic corrosive, methyl methacrylate)) delivered the medication by surface disintegration and considered total medication discharge. The medication and polymer structure a gel at a basic dampness level and at a related crucial time stretch ³⁹. Subsequently, any definition that can keep the medication and polymer from arriving at this the basic dampness level can help convey the medication effectively.

It has been accounted for that, for a given medication, the supersaturation rate is represented by the level of polymer dissolvability in the disintegration medium ⁴¹. This has been exhibited by looking at indomethacin SDS granules dependent on (a) water-insoluble polymers (i.e., ethylcellulose and Eudragit® RLPO), (b) polymers that are solvent just in acidic or fundamental conditions (i.e., Eudragit® E100, Eudragit® L100, and HPMC-AS), and (c) water-dissolvable polymers (i.e., PVP and Soluplus®) ⁴¹.

Impact of Manufacturing Process and Downstream Processing: The manufacturing process has a significant impact on the dosage form performance, and the assembling interaction essentially affects the dose structure execution and recrystallization. For instance, the assembling interaction may influence measurements structure porosity. The effect of porosity was explored by looking at low-porosity, thermally molded solid tablets to profoundly permeable, direct pressure tablets, where both tablet types had similar structure and measurements. The outcomes showed that permeable tablets containing PVP produced by direct pressure had inadequate delivery profiles in contrast with nonporous, thermally molded tablets ³⁴. In permeable tablets, the medication which is solubilized inside the pores of the tablet may display neighborhood supersaturation in the microenvironment, and this prompts drug precipitation. Shaped tablets showed a more slow pace of water dissemination comparative with tablets obtained by granule pressure. In the event that the water take-up rate is slower than the disintegration pace of the tablet, at that point, a zero-request delivery can be gotten.  Expanded delivery SDS typically require downstream preparation to acquire the last dose structure that can be directed to patients ⁴⁴. Such cycles (e.g., tablet pressure, granulation, covering) may prompt decreased actual dependability because of the presence of solvents or the use of mechanical energy. For example, wet granulation, which is normally utilized in the drug business to improve stream and pressure, accompanies a high danger of medication recrystallization because of the presence of a wetting specialist.  The mechanical pressure that happens during dry granulation that utilizes roller compaction can likewise prompt recrystallization ⁴⁶. To be sure, fundamentally higher crystallinity of ibipinabant was distinguished in tablets arranged by roller compaction in contrast with straightforwardly packed tablets. This is clarified by the higher number of pressure and granulating steps ⁴⁷.

The various fillers gave diverse actual soundness profiles, with microcrystalline cellulose giving the most steady profile. Expanded degrees of crystallinity were likewise seen in the covered tablets, and this was ascribed to the openness of the SDS to dampness and warmth. In this way, consideration ought to be given to guarantee the actual solidness of SDS during conclusive measurement structure production.

Approaches for Extended-release Solid Dispersions System:

• Approaches based on hydrophilic polymers
• Approaches based on hydrophobic polymers
• Approaches based on wax and lipid systems

Approaches based on Hydrophilic Polymers: Hydrophilic polymers are characterized as polymers that disintegrate or are swollen by water. They may contain polar or charged utilitarian gatherings and can be arranged dependent on their substance structure. Hydrophilic polymers have been generally researched in the assembling of SDS because of their high wettability ⁴⁹ and their capacity to keep up the medication in a supersaturated state ⁹. Hydrophilic polymers can be utilized as a transporter SDS or utilized as extended-discharge specialists, contingent upon the dose structure measurements, polymer science, dissolvability in the medium and the system of medication discharge ⁴⁴.

HPMC is the most generally utilized hydrophilic polymer for the extended arrival of medications from tablets ⁵⁰. It is accessible in an assortment of evaluations that depend on their levels of hydroxyl and methyl replacement and dependent on their atomic weight ⁵¹. Upon hydration, HPMC structures a hydrogel, which delivers the medication by dispersion ¹⁶. HPMC and itraconazole have been prepared by hot-dissolve expulsion to frame SDS granules that display a lethargic delivery rate ⁵². An HPMC-based detailing showed a more slow disintegration rate than granules made with Eudragit® E100 (cationic methacrylate polymer) or Eudragit E® 100-PVP. In any case, an in-vivo pharmacokinetic concentrate in people showed that the more gradually dissolving HPMC-based detailing had higher AUC esteem than the Eudragit® E100 and Eudragit E® 100-PVP plans. This was clarified by diminished itraconazole precipitation because of its more slow disintegration rate. This backs the case that a more slow medication discharge rate could help increment bioavailability sometimes.

Another way to deal with produce stretched-out discharge SDS is to fuse HPMC as a framework shaping specialist (i.e., in the outer stage) to pack recently made SDS into tablets ^{18, 55}. Utilizing this technique, an SDS that contains nimodipine and poloxamer 188 was processed and afterward mixed with HPMC alongside other excipients to work with tablet pressure ⁵⁶. Broadened discharge definitions help diminish the recurrence of organization of short half-life medications, for example, nimodipine. It has been accounted for that expanding measures of HPMC 15,000 came about in more slow medication discharge ^{16, 57}. Increasing the consistency by changing the HPMC grade additionally builds the disintegration season of the undefined medication ⁵⁸. The rate and degree of medication disintegration were expanded by the presence of HPMC-AS, which was utilized as a transporter for the SDS and advanced steadiness inside the tablet ⁵⁹.

Approaches based on Hydrophobic Polymers: Hydrophobic polymers come up short on a proclivity with water, and they normally show a static contact point of > 90° ⁶⁵. They are especially helpful in planning expanded delivery SDS since they forestall or defer hydration of the shape of the measurement and thus give actual solidness to drugs that are defenseless to recrystallization ⁶⁶. The components of the dose structure can be changed relying upon the hydrophobicity of the definition and the ideal medication discharge profile of the structure of the measurement, recently depicted, shows SDS granules containing indomethacin and ethylcellulose displayed a sluggish medication discharge rate ⁴¹; a tablet having a similar structure would have a much more slow, and likely imperfect, disintegration profile, in view of the bigger surface territory, comparative with volume, that is accessible for disintegration.

Disintegration profiles of SDS granules made of insoluble hydrophobic polymers, for example, ethylcellulose or Eudragit® RS, are not the same as granules made of solvent polymers, for example, Soluplus® or PVP because of the distinction in supersaturation rate, as clarified prior. Granules made of insoluble polymers keep away from the spring and parachute drug disintegration profile, however, they actually display supersaturation that can, at a given time, show more significant levels than the focus coming about because of hydrophilic granules ⁴¹. Hydrophobic polymers are additionally helpful in keeping a serious degree of supersaturation and forestalling recrystallization. As referenced before, HPMC-AS was better than HPMC in keeping up butylparaben supersaturation in impartial conditions because of moderate hydration and an exceptionally short dispersion way length ³⁸. HPMC-AS was additionally utilized as an SDS transporter to forestall glipizide recrystallization and was compacted with HPMC to fabricate Extended-discharge tablets ⁵⁸. Furthermore, hydrophobic and water-insoluble polymers that forestall hydration of the measurement structure are valuable to drugs that show issues identifying with acidic or enzymatic compound steadiness. The corruption of a disulfiram SDS during dis-integration in reproduced gastric liquid was forestalled by packing the medication containing SDS with Kollidon® SR, a non-swellable polymer dependent on the polyvinyl acetic acid derivation and povidone ⁵⁵.

Approaches based on Wax and Lipid Systems: Lipids are a class of natural mixtures that are ordered as waxes, glycerides, greasy alcohols, and unsaturated fats. Waxes, which are esters of unsaturated fats and long-chain alcohols ⁶⁹, were utilized as the base for deterioration frameworks that forestalled recrystallization inside the tablets ³⁵. The presence of the wax limited water retention to the tablet surface, in this way, forestalling drug recrystallization. A shower-dried SDS containing cilostazol and povidone was packed with hydrogenated vegetable oil as the wax framework previously and sodium carboxymethyl cellulose as the disintegrant. Upon surface hydration, the disintegrant swells, and the SDS granules drain out from the dose structure. Utilizing this framework, cilostazol discharge was controlled and arrived at the finish without recrystallization. The ideal definition followed Higuchi's delivery rate and steady. The delivery system was resolved to be dispersion from the lattice ³⁵.

The biodegradable properties of some lipid-based frameworks, including hydrogenated castor oil (HCO), can be utilized to make inserts for the subcutaneous conveyance of medication containing SDS. For instance, HCO was picked on the grounds that, besides its biodegradable properties, it is a successful excipient for Extended medication delivery, and its reasonableness decreases producing costs ⁷⁰. Utilizing a dissolve strategy, ivermectin was totally scattered in a nebulous state in HCO when the medication to-HCO proportion was at 1:3 or lower. This technique accomplished the all-encompassing arrival of the medication and disposed of burst discharge, which are two significant attributes for the all-encompassing arrival of a medication from an SDS.

In another examination, nanostructured lipid transporters made out of glyceryl monostearate and glyceryl monocaprylate were researched to support the arrival of nebulous raloxifene HCl nanoparticles. The nanostructured lipid transporters were produced utilizing the dissolvable dispersion strategy. A burst discharge was seen during the initial 8 h, trailed by an all-encompassing delivery for up to 36 h. This framework displayed improved bioavailability comparative with a medication suspension ⁷¹.

The in-vivo pharmacokinetic boundaries can be balanced by altering the molecule size or the precipitation temperature, the in vitro drug discharge rate from the lipid particles could be tuned for quick or broadened discharge by controlling either the molecule size or the precipitation temperature even in the wake of framing the medication lipid particles ⁷². A 24-h Extended-discharge profile displayed lower C max and delayed T max in contrast with a quick delivery, nano-organized lipid transporter.

CONCLUSION: Recently, several approaches have been proposed for formulating the solid dispersion extended release of drugs. These examinations center explicit difficulties, for example, the recrystallization of medications in their dose structure, which can be forestalled utilizing hydrophobic excipients or by disintegrating frameworks with decreased hydration of the structure of the measurement. Different difficulties have been discovered, for example, the low medication discharge brought about by low degrees of supersaturation, high hydrophobicity, or polymer and medication gelling.

The physiochemical properties of a medication (e.g., solvency, penchant for recrystallization) drastically affect plan execution. In this manner, they should be deliberately viewed when figuring broadened discharge type of a medication utilizing strong scattering. What's more, if appropriately planned, the all-inclusive arrival of a medication from a Solid scattering can diminish the reprecipitation of the medication hence, improving its bioavailability in people.

ACKNOWLEDGEMENT: Nil

CONFLICTS OF INTEREST: Nil

REFERENCES:

1. Siew A: Solving poor solubility to unlock a drug’s potential. Pharm Technol 2015; 39(7): 20-27.
2. Serajuddin AT: Salt formation to improve drug solubility. Adv Drug Deliv Rev 2007; 59(7): 603-16.
3. Good DJ and Rodríguez-Hornedo NR: Solubility advantage of pharmaceutical cocrystals. Cryst Growth Des 2009; 9: 2252-64.
4. Pouton CW: Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci 2006; 29(3-4): 278-87.
5. Dahan A, Miller JM, Hoffman A, Amidon GE and Amidon GL: The solubility-permeability interplay in using cyclodextrins as pharmaceutical solubilizers: mechanistic modeling and application to progesterone. J Pharm Sci 2010; 99(6): 2739-49.
6. Shah N, Sandhu H, Phuapradit W, Pinal R, Iyer R and Albano A: Development of novel micro precipitated bulk powder (MBP) technology for manufacturing stable amorphous formulations of poorly soluble drugs. Int J Pharm 2012; 438(1-2): 53-60.
7. Chiou WL and Riegelman S: Oral absorption of griseofulvin in dogs: increased absorption via solid dispersion in polyethylene glycol 6000. J Pharm Sci 1970; 59(7): 937-42.
8. Serajuddin AT: Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. J Pharm Sci 1999; 88(10): 1058-66.
9. Brouwers J, Brewster ME and Augustijns P: Supersaturating drug delivery systems: the answer to solubility-limited oral bioavailability J Pharm Sci 2009; 98(8): 2549-72.
10. Miller JM, Beig A, Carr RA, Spence JK and Dahan A: A win-win solution in oral delivery of lipophilic drugs: supersaturation via amorphous solid dispersions increases apparent solubility without sacrifice of intestinal membrane permeability. Mol Pharm 2012; 9(7): 2009-16.
11. Amidon GL, Lennernas H, Shah VP and Crison JR: A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995; 12(3): 413-20.
12. Friesen DT, Shanker R, Crew M, Smithey DT, Curatolo WJ and Nightingale JA: Hydroxypropyl Ethylcellulose acetate succinate-based spray-dried dispersions: an overview. Mol Pharm 2008; 5(6): 1003-19.
13. Breitenbach J: Melt extrusion: from process to drug delivery technology. Eur J Pharm Bio 2002; 54(2): 107-17.
14. Taylor LS and Zhang GG: Physical chemistry of supersaturated solutions and implications for oral absorption. Adv Drug Deliv Rev 2016; 101: 122-42.
15. Sun DD and Lee PI: Evolution of supersaturation of amorphous pharmaceuticals: the effect of rate of supersaturation generation. Mol Pharm 2013; 10(11): 4330-46.
16. Verreck G, Six K, Mooter GVD, Baert L, Peeters J and Brewster ME: characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose pepared by melt extrusion_part-1. 2003; 251(1-2): 165-74.
17. Siepmann J and Siepmann F: Modeling of diffusion controlled drug delivery. J Control Release 2012; 161(2): 351-62.
18. Nguyen TN, Tran PH, Van Vo T, Duan W and Truong-Dinh Tran T: Development of an Extended release solid dispersion using swellable polymer by melting method. Pharm Res 2016; 33(1): 102-9.
19. LaFountaine JS, Prasad LK, Miller DA, McGinity JW and Williams RO: Mucoadhesive amorphous solid dispersions for Extended release of poorly water-soluble drugs. Eur J Pharm Biopharm 2017; 113: 157-67.
20. Tres F, Treacher K, Booth J, Hughes LP, Wren SA and Aylott JW: Indomethacin-Kollidon VA64 extrudates: a mechanistic study of pH-dependent controlled release. Mol Pharm 2016; 13(3): 1166-75.
21. Crowley MM, Schroeder B, Fredersdorf A, Obara S, Talarico M and Kucera S: Physicochemical properties and mechanism of drug release from ethyl cellulose matrix tablets prepared by direct com-pression and hot-melt extrusion. Int J Pharm 2004; 269(2): 509-22.
22. 22 Wang S,liu C,Chen Y, Zhu AD and Quan F.aggregation of hydroxy propyl methyl cellulose acetate succinate under its dissolving PH and the impact on drug supersaturation. Mol Pharmaceutics 2018; 15(10): 4643-53.
23. Lipinski CA, Lombardo F, Dominy BW and Feeney PJ: Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. ADDR 2001; 46(1–3): 3-26.
24. Dokoumetzidis A and Macheras P: A century of dissolution research: from Noyes and Whitney to the biopharmaceutics classification system. Int J Pharm 2006; 321(1-2): 1-11.
25. Janssens S and Van den Mooter G: Review: physical chemistry of solid dispersions. J Pharm Pharmacol. 2009; 61(12): 1571-86.
26. LaMer V and Dinegar R: Theory, Production and Mechanism of Formation of Monodispersed Hydrosols. J Am Chem Soc 1950; 72: 4847-54.
27. Sarode AL, Wang P, Obara S and Wrthen DR: Supersaturation, nucleation, and crystal growth during single- and biphasic dissolution of amorphous solid dispersions: polymer effects and implications for oral bioavailability enhancement of poorly water-soluble drugs. Eur J Pharm Biopharm 2014; 86(3): 351-60.
28. Hilden LR and Morris KR: Physics of amorphous solids. J Pharm Sci 2004; 93(1): 3-12.
29. Hancock BC, Shamblin SL and Zografi G: Molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures. Pharm Res 1995; 12(6): 799-806.
30. Chokshi RJ, Shah NH, Sandhu HK, Malick AW and Zia H: Stabilization of low glass transition temperature indomethacin formulations: impact of polymer-type and its concentration. J Pharm Sci 2008; 97(6): 2286-98.
31. Vasanthavada M, Tong WQ, Joshi Y and Kislalioglu MS: Phase behavior of amorphous molecular dispersions I: determination of the degree and mechanism of solid solubility. Pharm Res 2004; 21(9): 1598-606.
32. Wang X, Michoel A and Van den Mooter G: Solid state characteristics of ternary solid dispersions composed of PVP VA64, Myrj 52 and itraconazole. Int J Pharm 2005; 303(1–2): 54-61.
33. Dajun D, Sun, Ping I and Lee: probing the mechanism of drug release from amorphous solid dispersions in medium-soluble and medium-insoluble carriers. Journal of Controlled Release 2015; 211: 85-93.
34. Keen JM, Hughey JR, Bennett RC, Jannin V, Rosiaux Y and Marchaud D: Effect of tablet structure on controlled release from supersaturating solid dispersions containing glyceryl behenate. Mol Pharm. 2015;12(1):120–6.
35. Verma S and Rudraraju VS: Disintegration mediated controlled release supersaturating solid dispersion formulation of an insoluble drug: design, development, optimization, and in-vitro AAPS Pharm Sci Tech 2015; 16(1): 85-97.
36. Goepferich A: Mechanisms of polymer degradation and erosion. Biomaterials 1996; 17(2): 103-14.
37. Pokharkar VB, Mandpe LP, Padamwar MN, Ambike AA, Mahadik RK and Paradkar A: Development, characterization and stabilization of amorphous form of a low Tg drug. Powder Technol 2006; 167(1): 20-5.
38. Tajarobi F, Larsson A, Matic H and Abrahmsen-Alami S: The influence of crystallization inhibition of HPMC and HPMCAS on model substance dissolution and release in swellable matrix tablets. Eur J Pharm Bio Pharm 2011; 78(1): 125-33.
39. Fan C, Pai-Thakur R, Phuapradit W, Zhang L, Tian H and Malick W: Impact of polymers on dissolution performance of an amorphous gelleable drug from surface-coated beads. Eur J Pharm Sci 2009; 37(1): 1-10.
40. Alderman D: A review of cellulose ethers in hydrophilic matrices for oral controlled-release dosage forms. Int J Pharm Technol Prod Manuf 1984; 5(3): 1-9.
41. Sun DD and Lee PI: Probing the mechanisms of drug release from amorphous solid dispersions in medium-soluble and medium-insoluble carriers. J Control Release 2015; 211: 85-93.
42. Sun DD, Ju TC and Lee PI: Enhanced kinetic solubility profiles of indomethacin amorphous solid dispersions in poly(2-hydroxyethylmethacrylate) hydrogels. Eur J Pharm Biopharm 2012; 81(1): 149-58.
43. Meng F, Meckel J and Zhang F: Investigation of itraconazole ternary amorphous solid dispersions based on povidone and Carbopol Eur J Pharm Sci 2017; 106: 413-21.
44. Demuth B, Nagy ZK, Balogh A, Vigh T, Marosi G and Verreck G: Downstream processing of polymer-based amorphous solid dispersions to generate tablet formulations. Int J Pharm 2015; 486(1-2): 268-86.
45. Jijun F, Lishuang X, Xiaoli W, Shu Z, Xiaoguang T and Xingna Z: Nimodipine (NM) tablets with high dissolution containing NM solid dispersions prepared by hot-melt extrusion. Drug Dev Ind Pharm 2011; 37(8): 934–44.
46. Nemet Z, Sztatisz J and Demeter A: Polymorph transitions of bicalutamide: a remarkable example of mechanical activation. J Pharm Sci 2008; 97(8): 3222-32.
47. Leane MM, Sinclair W, Qian F, Haddadin R, Brown A and Tobyn M: Formulation and process design for a solid dosage form containing a spray-dried amorphous dispersion of ibipinabant. Pharm Dev Technol 2013; 18(2): 359-66.
48. Finch CA: Hydrophilic polymers. In: Dyson RW, editor. Specialty polymers. Springer US; 1987: 65-82.
49. Vasconcelos T, Sarmento B and Costa P: Solid dispersions as strategy to improve oral bioavailability of poor water-soluble drugs. Drug Disc Today 2007; 12(23-24): 1068-75.
50. Li CL, Martini LG, Ford JL and Roberts M: The use of hypromellose in oral drug delivery. J Pharm Pharmacol 2005; 57(5): 533-46.
51. Rogers TL: Hypromellose. In: Rowe RC, Sheskey PJ, Quinn ME, editors. Handbook of pharmaceutical excipients. 6^th London: Pharmaceutical Press; 2009: 326-9.
52. Six K, Daems T, de Hoon J, Van Hecken A, Depre M and Bouche MP: Clinical study of solid dispersions of itraconazole prepared by hot-stage extrusion. Eur J Pharm Sci 2005; 24(2–3): 179-86.
53. Paaver U, Heinamaki J, Laidmae I, Lust A, Kozlova J and Sillaste E: Electrospun nanofibers as a potential controlled-release solid dispersion system for poorly water-soluble drugs. Int J Pharm 2015; 479(1): 252-60.
54. Sheth AR, Bates S, Muller FX, Grant DJW: Polymorphism in piroxicam. Cryst Growth Des 2004; 4: 1091-8.
55. Shergill M, Patel M, Khan S, Bashir A and McConville C: Development and characterisation of Extended release solid dispersion oral tablets containing the poorly water-soluble drug disulfiram. Int J Pharm 2016; 497(1-2): 3-11.
56. Lee HJ, Kim JY, Park SH, Rhee YS, Park CW and Park ES: Controlled-release oral dosage forms containing nimodipine solid dispersion and hydrophilic carriers. J Drug Deliv Sci Technol 37: 28-37.
57. Siepmann J and Peppas NA: Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). AdvDrug Deliv Rev 2001; 48(2-3): 139-57.
58. Lu Z, Yang Y, Covington RA, Bi YV, Durig T and Ilies MA: Supersaturated controlled release matrix using amorphous dispersions of glipizide. Int J Pharm 2016; 511(2): 957-68.
59. Lu Z, Yang Y, Covington RA, Bi YV, Durig T and Fassihi R: Amorphous-based controlled-release gliclazide matrix system. AAPS Pharm Sci Tech 2016; 18(5): 1699-709.
60. Tran PH, Tran TT, Piao ZZ, Vo TV, Park JB and Lim J: Physical properties and in-vivo bioavailability in human volunteers of isradipine using controlled release matrix tablet containing self-emulsifying solid dispersion. Int J Pharm 2013; 450(1-2): 79-86.
61. Lin Q, Fu Y, Li J, Qu M, Deng L and Gong T: A (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer)-dispersed Extended-release tablet for imperialine to simultaneously prolong the drug release and improve the oral bioavailability. Eur J Pharm Sci 2015; 79: 44-52.
62. Tran HT, Park JB, Hong KH, Choi HG, Han HK and Lee J: Preparation and characterization of pH-independent Extended re-lease tablet containing solid dispersion granules of a poorly water-soluble drug. Int J Pharm 2011; 415(1-2): 83-8.
63. Draganoiu E, Rajabi-Siahboomi A, Tiwari S, RoweRC, Sheskey PJ and Quinn ME: Handbook of pharmaceutical excipients. 6^th London: Pharmaceutical Press; 2009: 110-4.
64. Sun DD and Lee PI: Crosslinked hydrogels-a promising class of in-soluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs. Acta Pharm Sin B. 2014; 4(1): 26-36.
65. Law KY: Definitions for hydrophilicity, hydrophobicity, and superhydrophobicity: getting the basics right. J Phys Chem Lett 2014; 5(4): 686-8.
66. Desai J, Alexander K and Riga A: Characterization of polymeric dispersions of dimenhydrinate in ethyl cellulose for controlled release. Int J Pharm 2006; 308(1-2): 115-23.
67. Snejdrova E, Drastik M, Dittrich M, Kastner P and Nguyenova J: Mucoadhesive plasticized system of branched poly (lactic-co-glycolic acid) with aciclovir. Drug Dev Ind Pharm 2016; 42(10): 1653-9.
68. Dang N, Sivakumaran H, Harrich D, Shaw PN and Coombes AG: Evaluation of polycaprolactone matrices for Extended vaginal de-livery of nevirapine in the prevention of heterosexual HIV trans-mission. J Pharm Sci 2014; 103(7): 2107-15.
69. Jannin V, Rodier JD and Musakhanian J: Polyoxylglycerides and glycerides: effects of manufacturing parameters on API stability, excipient functionality and processing. IJP 2014; 466(1-2): 109-21.
70. Lu M, Xiong D, Sun W, Yu T, Hu Z and Ding J: Extended release ivermectin-loaded solid lipid dispersion for subcutaneous delivery: in-vitro and in-vivo Drug Deliv 2017; 24(1): 622-31.
71. Shah NV, Seth AK, Balaraman R, Aundhia CJ, Maheshwari RA and Parmar GR: Nanostructured lipid carriers for oral bioavailability enhancement of raloxifene: design and in vivo study. J Adv Res 2016; 7(3): 423-34.
72. Liu Y, Salituro GM, Lee KJ, Bak A and Leung DH: Modulating drug release and enhancing the oral bioavailability of torcetrapib with solid lipid dispersion formulations. AAPS Pharm Sci Tech 2015; 16(5): 1091-100.
    

    ---

    How to cite this article:

    Puhan KK, Raja S and Choudhary NK: Solid dispersion extended release system: a review. Int J Pharm Sci & Res 2021; 12(10): 5281-91. doi: 10.13040/IJPSR.0975-8232.12(10).5281-91.

    ---

    All © 2021 are reserved by the International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.