Dissolution Rate Of Solid Dispersion Research Articles

Solubility enhancement of antiprotozoal agent by solid dispersion and herbal tablet method to improve its rate of dissolution

Drug dissolution is the rate limiting step for bioavailability of poor aqueous soluble drug that consequently affects the in vivo drug absorption. In the present study solid dispersion based drug delivery system of Atovaquone were successfully developed in the form of tablets with improved dissolution characteristic by forming solid dispersion with PEG 4000. For the Atovaquone formulation, F1 was chosen as it has % drug release about 46 % in 180 min. FTIR spectra of drug with other excipients have not shown any interaction and also selected formulation was stable after stability studies. The in-vitro dissolution studies revealed a considerable boost in dissolution rate of Solid dispersions of Atovaquone in contrast to pure drug. From FTIR spectroscopy, it was concluded that there was no well-defined chemical interaction between Atovaquone and PEG 4000 in Solid dispersions, as no important new peaks could be observed. The Atovaquone solid dispersion based tablet (F1) showed 30.33% drug release within first 20 min. and 46.45% drug release within 180 min.Thus from studies, it could be concluded that solid dispersion of poor aqueous soluble Atovaquone by solvent evaporation technique were effectively formulate during PEG-4000 and PVP-K 30 hydrophilic polymers. Thus, the statement can be given that the rate of dissolution and solubility of poor aqueous soluble Atovaquon can be appreciably improved by solid dispersion by use of water soluble carriers by solvent evaporation technique.

PENINGKATAN DISOLUSI NIFEDIPIN DENGAN PELARUT PVP K-30 MENGGUNAKAN METODE DISPERSI PADAT

ABSTRACTNifedipine is an anti-hypertensive included in the Biopharmaceutics Classification System (BCS) class II to its nature of being poorly soluble in water, resulting in low bioavailability. One technique that can be used to improve the solubility of the dispersion technique. This research aimed to determine the effect of the concentration of PVP K-30 on physical characteristics, the dissolution rate of solid dispersions, and the interactions that occur between nifedipine with PVP K-30. The method of manufacturing solid dispersion is a melting-solvent method. FI - F III is a solid dispersion and F IV-VI F is a physical mixture. Formula used is the ratio of nifedipine: PVP K-30 FI (10%: 90%), F II (20%: 80%), F III (30%: 70%), F IV (10%: 90%), FV (20%: 80%), F VI (30%: 70%), and used as a control of pure nifedipine. Testing was conducted on the organoleptic test, flow rate, moisture content, melting point, dissolution testing, and FT-IR analysis. Dissolution test parameters used C (20). The data was obtained and analyzed by non-parametric test KruskalWallis and Mann-Whitney with a level of 95%. The results showed that solid dispersions aregranulated, yellow, and have a free-flowing nature. Test results C (20) FI, F II, F III, F IV, FV, F VI, and controls respectively were 89,48%; 51,75%; 22,58%; 12,88%; 24,07%; 26,34%; 24,95%. The results showed that the FI has the highest dissolved. Results of FT-IR spectra showed no interaction between nifedipine with PVP K-30.Keywords: dissolution, nifedipine, PVP K-30, solid dispersion

PharmSD: A novel AI-based computational platform for solid dispersion formulation design

Solid dispersion is an effective way to improve the dissolution and oral bioavailability of water-insoluble drugs. To obtain an effective solid dispersion formulation, researchers need to evaluate a series of important properties of the designed formulation, including in vitro dissolution and physical stability of solid dispersion. It is usually time-consuming and labor-intensive to explore these properties by traditional experimental methods. However, the development of machine learning technology provides a powerful way to solve such problems. By using advanced machine learning algorithms, we established a series of robust models and finally formed a systematic strategy to assist the formulation design. Based on these works, we developed a new formulation prediction platform of solid dispersion: PharmSD. This platform provides efficient functionalities for the prediction of physical stability, dissolution type and dissolution rate of solid dispersion independently. Then, a virtual screening pipeline can be produced by considering those prediction results as a whole, which enables users to filter different kinds of drug-polymer combinations in various experimental situations and figure out which combination could form the best formulation. Moreover, it also provides two tools that enable researchers to evaluate the application domain of models and calculate the similarity of dissolution curves. PharmSD is expected to be the first freely available web-based platform that is fully designed for the formulation design of solid dispersion driven by machine learning. We hope this platform could provide a powerful solution to assist the formulation design in the related research area. It is available at: http://pharmsd.computpharm.org.

Development of Apremilast Solid Dispersion Using TPGS and PVPVA with Enhanced Solubility and Bioavailability.

Apremilast (APST) is an effective inhibitor of phosphodieasterase 4 (PDE4) which is the first oral drug for the treatment of adult patients with active psoriatic arthritis. However, Apremilast's low solubility restricts its dissolution and bioavailability. In this study, APST solid dispersion with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and Poly(1-vinylpyrrolidone-co-vinyl acetate) (PVPVA) was developed to improve the dissolution and bioavailability of APST by spray drying. A series of TPGS were synthesized to elucidate the effect of the ratio of monoester to diester on solubilizing capacity. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectrophotometry (FT-IR) were used to characterize the solid dispersion, and the results showed that APST was amorphous in solid dispersion. In vitro dissolution study showed that the dissolution rate of solid dispersion in phosphate buffered saline (pH 6.8) was remarkably increased, reaching a release of 90% within 10 min. Moreover, in vivo pharmacokinetics study revealed that the bioavailability of solid dispersion in rats had significant improvement. In particular, its Cmax and AUClast were nearly 22- and 12.9-fold greater as compared to APST form B, respectively. In conclusion, APST solid dispersion with TPGS and PVPVA is an alternative drug delivery system to improve the solubility and oral bioavailability of APST.

Insoluble Polymers in Solid Dispersions for Improving Bioavailability of Poorly Water-Soluble Drugs.

In recent decades, solid dispersions have been demonstrated as an effective approach for improving the bioavailability of poorly water-soluble drugs, as have solid dispersion techniques that include the application of nanotechnology. Many studies have reported on the ability to change drug crystallinity and molecular interactions to enhance the dissolution rate of solid dispersions using hydrophilic carriers. However, numerous studies have indicated that insoluble carriers are also promising excipients in solid dispersions. In this report, an overview of solid dispersion strategies involving insoluble carriers has been provided. In addition to the role of solubility and dissolution enhancement, the perspectives of the use of these polymers in controlled release solid dispersions have been classified and discussed. Moreover, the compatibility between methods and carriers and between drug and carrier is mentioned. In general, this report on solid dispersions using insoluble carriers could provide a specific approach and/or a selection of these polymers for further formulation development and clinical applications.

Study of the Solubility of Furazolidone from Solid Dispersions with Polyvinylpyrrolidone

The effect of solid dispersions (SDs) on the solubility of furazolidone is studied. Furazolidone and its SDs with polyvinylpyrrolidone (PVP), PVP-10 000, PVP-12 600, and PVP-24 000 are examined. When using SDs, the solubility and dissolution rate of the nitrofuran derivative is increased. The solubility of furazolidone from SD is increased by a factor of 1.1 to 1.6. The dissolution rate of SDs is increased by a factor of 1.8 to 2.8. The complex of physicochemical methods of investigation suggests that an increase in solubility from SDs is caused by the loss of crystallinity and the formation of a solid solution of furazolidone during the preparation of SDs, as well as the solubilizing effect of the polymer during the subsequent dissolution of the SD in water. The results can be used in the development of hydrophilic soft and fast dissolving solid dosage forms of furazolidone with increased release and bioavailability.

Solubility improvement of Lapatinib by Novel Techniques of Solid Dispersion

Objective: Tyrosine kinase inhibitor, Lapatinib (LAP) is highly lipophilic in nature and presents challenges with regard to its low and variable oral bioavailability. Polymer-based solid dispersion technology has been considered as the major advancement in overcoming limited aqueous solubility and oral absorption issues. In the present research work, approaches were taken to improve the dissolution characteristics of LAP by developing suitable systems of solid dispersion. Methods: Solid dispersions of lapatinib were prepared utilizing techniques like solvent controlled coprecipitation, fusion, nanoprecipitation and spray drying. Polymers with different ionic characteristics like Eudragit® EPO (cationic), Eudragit® L 100 55 (anionic), HPMCP HP 55 (anionic), HPMC AS (anionic) and Povidone K 30 (non-ionic) were employed at three different ratios of 1:1, 1:2 and 1:3 to prepare the solid dispersions of weakly basic lapatinib. Dissolution study in media corresponding to different physiologically relevant pH was performed to understand the effectiveness of the technique and effect of the polymer. Additionally, samples were also subjected for X-ray powder diffraction study to understand the nature of the drug in the solid dispersion systems. Results: It was observed that irrespective of the pH of the dissolution media, the dissolution rate of solid dispersions of LAP prepared with anionic polymers in particular HPMCP HP 55 is more which is attributed to the weakly basic nature of lapatinib. The diffractograms show substantial decrease in the crystallinity of lapatinib in the solid dispersions. Conclusion: The combination of solid dispersion technique with supersaturable systems appears to hold promise for improving dissolution and bioavailability of poorly soluble drugs. Solid dispersions significantly increase dissolution of LAP, which can be a starting point of a new LAP formulation with improved bioavailability. The selection of polymers that can inhibit crystallization of LAP in a supersaturated state becomes the key factor for an effective formulation. The present work is an attempt in this direction.

Screen for Inhibitors of Crystal Growth to Identify Desirable Carriers for Amorphous Solid Dispersions Containing Felodipine.

The solvent-shift method was used to identify appropriate polymers that inhibit the growth of felodipine crystals by monitoring particle size in supersaturated drug solutions in the presence of different polymers. We speculated that there would be an intermolecular interaction between the selected polymer (zein) and felodipine by extrapolating the inhibitory effect on crystal growth and then used the selected polymer as a carrier to prepare solid dispersions. The formulations were characterized by crystalline properties, thermodynamics of mixing, dissolution behavior, and physical stability. Powder x-ray diffraction and differential scanning calorimetry experiments indicated that amorphous solid dispersions were formed when the proportion of felodipine was < 30% (w/w). Stability tests showed that a solid dispersion with 20% felodipine remained in an amorphous state and was stable under accelerated storage conditions for 6months. The dissolution rates of solid dispersions were significantly greater than those of the active pharmaceutical ingredient or physical mixtures. Analysis by Fourier-transform infrared spectroscopy and Raman microspectroscopy indicated the formation of intermolecular interactions between zein and felodipine. The study demonstrates the successful application of the chosen polymer as a carrier in solid dispersions and validates the concept of extrapolating the inhibitory effect on crystal growth to intermolecular interactions.

Improvement in Dissolution of Bosentan Monohydrate by Solid Dispersions Using Spray Drying Technique

Background: Bosentan monohydrate (BM), a dual endothelin receptor antagonist, is indicated for the treatment of patients with pulmonary arterial hypertension (PAH). It is poorly soluble in water, and having absolute bioavailability of 50%. Objective: The aim of the present work is to develop and evaluate the solid dispersions (SD) of a poorly water soluble drug bosentan monohydrate (BM). Method: Solid dispersions (SDs) systems of BM were prepared with Hydroxy propyle β-cyclodextrin (HPβ-CD) and Polyethylene glycol (PEG-4000) polymers using a spray drying technique. Result: The significant rise in a saturation solubility 174.23±1.36 mg/mL; and drug dissolution 95.11±1.22%; was observed with optimized formulation (SD 6). The solid state characterization of optimized formulation (SD 6) by SEM, DSC, and XRPD revealed the absence of crystalline nature of BM in solid dispersion. High dissolution rate of solid dispersion (SD 6) compared with pure drug indicated the increase in dissolution characteristics. Conclusion: In conclusion, our studies illustrated that spray drying technique could be useful large scale producing method to prepare the solid dispersion of bosentan with HP β-CD, which can improve the solubility as well as stability of the formulation.

Development of a binary carrier system consisting polyethylene glycol 4000 - ethyl cellulose for ibuprofen solid dispersion.

Background and Objective:One of the established strategies to improve solubility and dissolution rate of poorly water-soluble drugs is solid dispersion (SD). Polyethylene glycol (PEG) is used as common carrier despite its stability problem which may be overcome by the addition of hydrophobic polymer. The present research aimed to develop an SD formulation with ibuprofen, a poor water-soluble BCS Class II drug as active pharmaceutical ingredient (API) and PEG 4000-ethyl cellulose (EC) as binary carrier.Methods:Melt mixing SD method was employed using a ratio of API: binary carrier (1:3.5 w/w) (SDPE). Another SD was prepared using only PEG (SDP) as a carrier for comparative study. The developed formulation was evaluated using optical microscopy, scanning electron microscopy (SEM), determination of moisture content, differential scanning calorimetry (DSC), in vitro dissolution test, attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and flow properties.Results:SEM and DSC indicated the conversion of crystalline ibuprofen to fine partly amorphous solid dispersion, which was responsible for the increase in dissolution rate of SD than a physical mixture. The release characteristics within 1 h from the higher to the lower value were the SDPE> SDP> physical mixture. Flow property evaluation using the angle of repose showed no difference between SD and PM. However, by Carr index and Hausner ratio, the flow properties of SDPE was excellent.Conclusion:The SD formulation with the PEG 4000-EC carrier can be effective to enhance in vitro dissolution of ibuprofen immediate release dosage form.

PVP 첨가에 의해 제조된 올메사탄 메독소밀 고체분산체의 방출패턴 연구

올메사탄은 BCS 2단계에 해당하는 약물로 물에 잘 녹지 않는 난용성 약물이다. 이런 약물이 낮은 생체이용률과 제형을 설계하는 과정에서 어려움을 주는 원인이 된다. 본 연구에서는 올메사탄을 분무건조법 및 회전용매증 발법을 이용해 고체분산체를 제조하여 제법에 따른 난용성약물의 용출률을 확인하였다. 수용성 고분자로 PVP를 사용하여 약물과 고분자의 비율별로 고체분산체를 제조하였다. SEM을 이용하여 고체분산체의 형태학적인 특성을 분석하였고, 고체분산체의 결정학적 성질은 XRD와 DSC를 통하여 확인하였다. 또한 FTIR을 통해 화학적인 변화를 확인하고, 생체 외 용출거동 실험을 통하여 변화된 용출률을 확인하였다. 제조된 고체분산체는 pH 1.2에서 용출을 확인하였으며, 올메텍과 용출률을 비교하였으며, 분무건조를 통해 약물의 용출률을 향상시킬 수 있다는 것을 확인할 수 있다. Olmesartan affiliated to biopharmaceutics classification system class 2 is a poorly water soluble drug. For this reason, olmesartan showed a low bioavailability and a lot of difficulties in the process of designing the pharmaceutical formulation. We prepared the solid dispersions of olmesartan. We confirmed the dissolution rate of drug which was prepared by manufacturing. The pharmaceutical formulation of solid dispersions was designed by using PVP as water soluble polymer. We analyzed morphological feature of solid dispersion by employing a scanning electron microscope. Then, the crystalline property of solid dispersion was confirmed through X-ray diffraction and differential scanning calorimeter. Also, the chemical change of solid dispersion was confirmed by the Fourier transform infrared spectroscopy. In vitro dissolution test was used to analyze the dissolution rate of solid dispersion. The prepared solid dissolution olmesartan confirmed the dissolution rate in the pH 1.2. It was compared with olmetec and improved dissolution rate through solid dispersion.

Ternary Solid Dispersions of Celecoxib: from Physical Characterization to Dissolution Enhancement

The poor solubility and wettability of a non steroidal anti inflammatory drug, celecoxib leads to poor dissolution and hence, low bioavailability after oral administration. The objective of the present study was to formulate solid dispersions of celecoxib, with water soluble polymers poly vinyl pyrrolidine (PVP K30), poly ethylene glycol (PEG 6000), hydroxypropyl methylcellulose 5cps (HPMC) and a super disintegrant namely pregelatinised starch (PGS) by common solvent and solvent evaporation methods. Solid Dispersions prepared were evaluated for dissolution rate and dissolution efficiency in comparison to the corresponding pure drug. Solid dispersions of celecoxib showed a marked enhancement in dissolution rate and dissolution efficiency. The increasing order of dissolution rate of solid dispersions of celecoxib with various polymers was HPMC > PVP > PEG. Solid dispersions at 2:2:6 ratio of C: HPMC: PGS, a 53.57 fold increase in the dissolution rate of celecoxib was observed. Solid dispersions were characterized by infrared spectroscopy (IR), differential scanning calorimetry (DSC) and X-ray diffractogram (XRD). Solid dispersions in combined carriers gave much higher rates of dissolution than super disintegrant PGS alone. Super disintegrant PGS alone or in combination with hydrophilic polymers could be used to enhance the dissolution rate of poorly soluble drug celecoxib. Finally, in-vitro dissolution studies showed that celecoxib release was greatly improved by formation of solid dispersion.

PREPARATION AND CHARACTERIZATION OF SOLID DISPERSIONS OF CARVEDILOL WITH POLOXAMER 188

Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. The poor solubility of carvedilol leads to poor dissolution and hence variation in bioavailability. The purpose of the present investigation was to increase the solubility and dissolution rate of carvedilol for enhancement of oral bioavailability. In the present investigation solid dispersions with poloxamer 188 were prepared by fusion method. The physical mixture and solid dispersion(s) were characterized for drug-carrier interaction, drug content, solubility and dissolution rate. The solubility of drug increased with increasing polymer concentration. The dissolution rate was substantially improved for carvedilol from its solid dispersion compared with pure drug and physical mixture. As indicated from X-ray diffraction pattern, DSC thermograms and SEM photographs, carvedilol was in the amorphous form, which confirmed the better dissolution rate of solid dispersions. FTIR results proved no chemical interaction between carvedilol and poloxamer 188. SEM images showed a novel morphology of solid dispersion compared with pure drug. The solid dispersion was stable under accelerated storage conditions.

Molecular Effect of PVP on The Release Property of Carvedilol Solid Dispersion

【This study aimed to confirm the effect of molecular weight (MW) in solid dispersion of carvedilol with poly-vinylpyrrolidone (PVP) of various MW. Solid dispersion of carvedilol with PVP was prepared by spray-drying method. Scanning electron microscopy (SEM) was used to analyze the surface of solid dispersion samples. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to analyze the crystalline of solid dispersion. Fourier transform infrared spectroscopy (FT-IR) was used to analyze the change of chemical structure characteristic of solid dispersion. DSC and XRD show that drug crystalline was changed. FT-IR revealed that chemical structure of solid dispersion comparing the chemical structure of drug was changed. The dissolution studies of solid dispersion presented at simulated gastric juice (pH 1.2). The dissolution rate of solid dispersion was dramatically enhanced than pure drug and the MW of PVP has an effect on the release property of carvedilol in solid dispersion. In conclusion, the present study has confirmed the effect of MW of PVP on release property of solid dispersion formulation of carvedilol with PVP.】

Solid Dispersions as a Drug Delivery System

ABSTRACT − Solid dispersion, defined as the dispersion of one or more active ingredient in a carrier or matrix at solidstate, is an efficient strategy for improving dissolution of poorly water-soluble drugs for enhancement of their bioavailabilit y.Compared to other conventional formulations such as tablets or capsules, solid dispersion which can be prepared by variousmethods has many advantages. However, despite numerous studies which have been carried out, limitations for com-mercializing these products remain to be solved. For example, during the manufacturing process or storage, amorphous formof solid dispersion can be converted into crystalline form. That is, the dissolution rate of solid dispersion would continuouslydecrease during storage, resulting in a product of no value. To resolve these problems, studies have been conducted on theeffects of excipients. In fact, modification of the solid dispersions to overcome these disadvantages has progressed from thefirst generation to the recent third generation products. In this review, an overview on solid dispersions in general will begiven with emphasis on the various manufacturing processes which include the use of polymers and on the stabilizationstrategies which include methods to prevent crystallization.Key words

Physicochemical characterization of finasteride:PEG 6000 and finasteride:Kollidon K25 solid dispersions, and finasteride: β-cyclodextrin inclusion complexes

Finasteride is a practically insoluble in water drug that belongs to the Class II of the BCS (poor solubility and high permeability). Solid dispersions are solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug. Solid dispersions are a successful strategy to improve drug release of poorly water-soluble drugs such as finasteride. Natural cyclodextrins are doughnut-shaped molecules with an internal hydrophobic cavity and a hydrophilic external surface. The lipophilic cavity enables cyclodextrins to form non-covalent inclusion complexes with a wide variety of poorly water-soluble drugs such as finasteride. The aim of this study was to investigate the formation of finasteride:PEG 6000 and finasteride:Kollidon K25 solid dispersions and finasteride:β-cyclodextrin inclusion complexes by solvent evaporation method using a mixture of water:ethanol (1:1). The formation of finasteride:PEG 6000 and finasteride:Kollidon K25 solid dispersions and finasteride:β-cyclodextrin inclusion complexes was investigated and characterized by differential scanning calorimetry (DSC), infrared (IR) spectroscopy, and dissolution studies from capsules containing a quantity equivalent to 5 mg of finasteride. The DSC thermograms revealed the transformation of finasteride into the amorphous state in solid dispersions with PEG 6000 and Kollidon K25, and in inclusion complexes with β-cyclodextrin. The IR spectra demonstrated molecular interaction in solid dispersions of finasteride with PEG 6000, and in inclusion complexes with β-cyclodextrin. Dissolution rate of solid dispersions and inclusion complexes was significantly greater than that of corresponding physical mixtures and pure drug, indicating that the formation of solid dispersions and inclusion complexes increased the solubility of the poorly soluble drug, finasteride.

분무건조기를 이용한 아토르바스타틴 고체분산체의 용출율 개선

Solid dispersions of poorly water-soluble drug, atorvastatin, were prepared with Eudragit L100 to improve the solubility by spray dryer. To investigate the correlation between physicochemical properties and dissolution rate of solid dispersions, the samples were characterized by scanning electron microscopy (SEM), differential scanning calorimeter (DSC) and fourier transform infrared spectroscopy (FT-IR). SEM and DSC were found that atorvastatin is amorphous in the Eudragit L100 solid dispersion. FT-IR was used to analyze the salt formation by interaction between atorvastatin and Eudragit L100. The dissolution rate of solid dispersed atorvastatin was markedly increased compared to drug powder in stimulated intestinal juice (pH 6.8). Thus, the solid dispersed atorvastatin using the spray drying method with Eudragit L100 may be effective for the bioavailability.

Evaluation of SLS: APG Mixed Surfactant Systems as Carrier for Solid Dispersion

The present investigation aims at studying the effect of mixed surfactant system of sodium lauryl sulphate (SLS) and alkyl polyglucosides (C(10)APG, C(12)APG and C(12/14)APG) on dissolution rate enhancement of poorly water soluble drug. Aceclofenac--a non-steroidal anti-inflammatory agent was used as a model drug as it has limited water solubility. The influence of the surfactant concentration in various blends on dissolution rate of Solid Dispersion (SD), prepared using solution method with ethanol as the solvent was studied and the advantage of mixed surfactant systems over the individual surfactants was illustrated by differences in the in-vitro dissolution profiles of SD. Physico chemical evaluation (critical micellar concentration, zeta potential and beta-parameter calculations) was carried out to study the mixed surfactant systems. Solid mixtures were characterized by Infrared spectroscopy (FT-IR); X-ray diffraction studies (XRD) and scanning electron microscopy (SEM). It was seen that the dissolution rate of aceclofenac from SD increased with the increase in the APG proportion relative to SLS with the optimum ratio of 0.2 SLS:0.8 APG showing the best effect in all cases. Results obtained from physico-chemical evaluation (the decrease in the value of critical micelle concentration and higher negative value of beta-parameters) suggested the existence of synergism between surfactants blends. The observed results in the dissolution rate enhancement could be attributed to the drug--surfactant interactions as evident from FT-IR, SEM and XRD results.

Preparation and characterization of etoricoxib solid dispersions using lipid carriers by spray drying technique

The basic objectives of this study were to prepare and characterize solid dispersions of poorly water-soluble drug etoricoxib using lipid carriers by spray drying technique. The properties of solid dispersions were studied by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), differential scanning calorimetry (DSC), hot-stage microscopy (HSM), radiograph powder diffraction (XRPD), and dissolution studies. The absence of etoricoxib peaks in XRPD profiles of solid dispersions suggests the transformation of crystalline etoricoxib into an amorphous form. In the HSM examination of solid dispersions, the dissolution of drug in the lipid carriers was observed, which was also confirmed by the absence of etoricoxib peak in DSC curves of solid dispersions. The DRIFTS spectra revealed the presence of hydrogen bonding in solid dispersions. The in vitro dissolution test showed a significant increase in the dissolution rate of solid dispersions as compared with pure etoricoxib, spray-dried etoricoxib, and physical mixtures of drug with lipid carriers. Therefore, the dissolution rate of poorly water-soluble drug etoricoxib can be significantly enhanced by the preparation of solid dispersions using lipid carriers by spray drying technique.

Stability study of amorphous valdecoxib

Formulation of poorly water-soluble drugs in the most stable dosage form for oral delivery perhaps presents the greatest challenge to pharmaceutical industry. Physical transformation of drug substance into its more soluble but metastable amorphous form is one of the approaches for improving dissolution rate of such drugs. The present study utilizes technique of spray drying for preparation of solid dispersions (SDs) and includes stability study of the same. Valdecoxib (VLD), a prototype of poorly water-soluble drugs, has been the drug of choice. The hydrophilic carriers selected were polyvinylpyrrolidone K30 (PVP) and hydroxypropylcellulose (HPC). SDs and pure VLD in the form of spray dried powder (SDVLD) in comparison with pure drug and corresponding physical mixtures (PMs) were initially characterized and then subjected to stability testing at ambient temperature and relative humidity up to 3 months. During initial characterization, increase in saturation solubility and dissolution rate was observed in all samples. DSC and XRPD studies of SDVLD and SDs suggested generation of amorphous form of drug. IR spectroscopy revealed presence of hydrogen bonding in SDs. During stability testing, there was gradual decrease in saturation solubility and dissolution rate of SDs, over the period of 3 months. While, saturation solubility of SDVLD dropped drastically within 15 days and was almost comparable with pure VLD. SD PVP retained the amorphous form of drug throughout stability period, whereas SD HPC and SDVLD presented incidence of crystallinity after 1 month and 15 days, respectively. This was justified by enthalpy relaxation studies in which, amorphous VLD showed considerable relaxation of enthalpy at T g, while it was totally suppressed in SD PVP and partly in SD HPC. The study thus definitely reveals tremendous potential of solid dispersions of valdecoxib with PVP, from stability point of view.