Evaluation of Drug Load and Polymer by Using a 96-Well Plate Vacuum Dry System for Amorphous Solid Dispersion Drug Delivery

It is well recognized that poor dissolution rate and solubility of drug candidates are key limiting factors for oral bioavailability. While numerous technologies have been developed to enhance solubility of the drug candidates, poor water solubility continuously remains a challenge for drug delivery. Among those technologies, amorphous solid dispersions (SD) have been successfully employed to enhance both dissolution rate and solubility of poorly water-soluble drugs. This research reports a high-throughput screening technology developed by utilizing a 96-well plate system to identify optimal drug load and polymer using a solvent casting approach. A minimal amount of drug was required to evaluate optimal drug load in three different polymers with respect to solubility improvement and solid-state stability of the amorphous drug-polymer system. Validation of this method was demonstrated with three marketed drugs as well as with one internal compound. Scale up of the internal compound SD by spray drying further confirmed the validity of this method, and its quality was comparable to a larger scale process. Here, we demonstrate that our system is highly efficient, cost-effective, and robust to evaluate the feasibility of spray drying technology to produce amorphous solid dispersions.     

Preparation and Evaluation of Solid Dispersions of A New Antitumor Compound Based on Early-Stage Preparation Discovery Concept

Ensuring sufficient drug solubility is a crucial problem in pharmaceutical-related research. For water-insoluble drugs, various formulation approaches are employed to enhance the solubility and bioavailability of lead compounds. The goal of this study was to enhance the dissolution and absorption of a new antitumor lead compound, T-OA. Early-stage preparation discovery concept was employed in this study. Based on this concept, a solid dispersion system was chosen as the method of improving drug solubility and bioavailability. Solid dispersions of T-OA in polyvinylpyrrolidone (PVP) K30 were prepared by the solvent evaporation method. Dissolution testing determined that the ideal drug-to-PVP ratio was 1:5. X-ray diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry were employed to confirm the formation of solid dispersions. Scanning electron microscopy demonstrated that T-OA was converted into an amorphous form. Both in vitro dissolution testing and the in vivo studies demonstrated that the solubility and bioavailability of T-OA were significantly improved when formulated in a solid dispersion with PVP. The dissolution rate of the T-OA/PVP solid dispersion was greatly enhanced relative to the pure drug, and the relative bioavailability of T-OA solid dispersions was found to be 392.0%, which is 4-fold higher than the pure drug.     

粉末包衣技术在药物制剂领域的应用研究进展

粉末包衣技术是薄膜包衣技术发展至今的一个重要分支,其在药物制剂领域的应用优势突出,近年来受到药剂学研究者的广泛关注。分类综述目前应用于药物制剂的几种主要粉末包衣技术,包括属于物理化学法中的凝聚法、溶剂蒸发法和熔融分散法以及物理机械法中的喷雾干燥法、喷雾冷凝法、干法包衣技术和气流悬浮包衣技术,并探讨粉末包衣技术的主要功用,如用于制备缓控释制剂、药物粉末表面改性、改善口服制剂感官效果和提高药物及制剂稳定性等。     

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), hotstage 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 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. Published: October 19, 2005     

Application of Carrier and Plasticizer to Improve the Dissolution and Bioavailability of Poorly Water-Soluble Baicalein by Hot Melt Extrusion

The objective of this study was to develop a suitable formulation for baicalein (a poorly water-soluble drug exhibiting high melting point) to prepare solid dispersions using hot melt extrusion (HME). Proper carriers and plasticizers were selected by calculating the Hansen solubility parameters, evaluating melting processing condition, and measuring the solubility of obtained melts. The characteristic of solid dispersions prepared by HME was evaluated. The dissolution performance of the extrudates was compared to the pure drug and the physical mixtures. Physicochemical properties of the extrudates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Relative bioavailability after oral administration in beagle dogs was assessed. As a result, Kollidon VA64 and Eudragit EPO were selected as two carriers; Cremophor RH was used as the plasticizer. The dissolution of all the extrudates was significantly improved. DSC and PXRD results suggested that baicalein in the extrudates was amorphous. FTIR spectroscopy revealed the interaction between drug and polymers. After oral administration, the relative bioavailability of solid dispersions with VA64 and EPO was comparative, about 2.4- and 2.9-fold greater compared to the pure drug, respectively.

Figure

Open in a separate windowᅟKEY WORDS: baicalein, carrier, high melting point, hot melt extrusion, plasticizer, solid dispersion     

The Stabilization of Amorphous Zopiclone in an Amorphous Solid Dispersion

Zopiclone is a poorly soluble psychotherapeutic agent. The aim of this study was to prepare and characterize an amorphous form of zopiclone as well as the characterization and performance of a stable amorphous solid dispersion. The amorphous form was prepared by the well-known method of quench-cooling of the melt. The solid dispersion was prepared by a solvent evaporation method of zopiclone, polyvinylpyrrolidone-25 (PVP-25), and methanol, followed by freeze-drying. The physico-chemical properties and stability of amorphous zopiclone and the solid dispersion was studied using differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), hot-stage microscopy (HSM), X-ray diffractometry (XRD), solubility, and dissolution studies. The zopiclone amorphous solid-state form was determined to be a fragile glass; it was concluded that the stability of the amorphous form is influenced by both temperature and water. Exposure of amorphous zopiclone to moisture results in rapid transformation of the amorphous form to the crystalline dihydrated form. In comparison, the amorphous solid dispersion proved to be more stable with increased aqueous solubility.KEY WORDS: amorphous, fragile, solid dispersion, stability, zopiclone     

Biomimetic Dissolution: A Tool to Predict Amorphous Solid Dispersion Performance

The presented study describes the development of a membrane permeation non-sink dissolution method that can provide analysis of complete drug speciation and emulate the in vivo performance of poorly water-soluble Biopharmaceutical Classification System class II compounds. The designed membrane permeation methodology permits evaluation of free/dissolved/unbound drug from amorphous solid dispersion formulations with the use of a two-cell apparatus, biorelevant dissolution media, and a biomimetic polymer membrane. It offers insight into oral drug dissolution, permeation, and absorption. Amorphous solid dispersions of felodipine were prepared by hot melt extrusion and spray drying techniques and evaluated for in vitro performance. Prior to ranking performance of extruded and spray-dried felodipine solid dispersions, optimization of the dissolution methodology was performed for parameters such as agitation rate, membrane type, and membrane pore size. The particle size and zeta potential were analyzed during dissolution experiments to understand drug/polymer speciation and supersaturation sustainment of felodipine solid dispersions. Bland-Altman analysis was performed to measure the agreement or equivalence between dissolution profiles acquired using polymer membranes and porcine intestines and to establish the biomimetic nature of the treated polymer membranes. The utility of the membrane permeation dissolution methodology is seen during the evaluation of felodipine solid dispersions produced by spray drying and hot melt extrusion. The membrane permeation dissolution methodology can suggest formulation performance and be employed as a screening tool for selection of candidates to move forward to pharmacokinetic studies. Furthermore, the presented model is a cost-effective technique.     

Use of Polyvinyl Alcohol as a Solubility Enhancing Polymer for Poorly Water-Soluble Drug Delivery (Part 2)

The KinetiSol® Dispersing (KSD) technology has enabled the investigation into the use of polyvinyl alcohol (PVAL) as a concentration enhancing polymer for amorphous solid dispersions. Our previous study revealed that the 88% hydrolyzed grade of PVAL was optimal for itraconazole (ITZ) amorphous compositions with regard to solid-state properties, non-sink dissolution performance, and bioavailability enhancement. The current study investigates the influence of molecular weight for the 88% hydrolyzed grades of PVAL on the properties of KSD processed ITZ:PVAL amorphous dispersions. Specifically, molecular weights in the processable range of 4 to 18 mPa · s were evaluated and the 4-88 grade provided the highest AUC dissolution profile. Amorphous dispersions at 10, 20, 30, 40, and 50% ITZ drug loads in PVAL 4-88 were also compared by dissolution performance. Analytical tools of diffusion-ordered spectroscopy and Fourier transform infrared spectroscopy were employed to understand the interaction between drug and polymer. Finally, results from a 30-month stability test of a 30% drug loaded ITZ:PVAL 4-88 composition shows that stable amorphous dispersions can be achieved. Thus, this newly enabled polymer carrier can be considered a viable option for pharmaceutical formulation development for solubility enhancement.KEY WORDS: amorphous solid dispersion, itraconazole, polyvinyl alcohol, PVAL, solubility enhancement     

Co-solvent Evaporation Method for Enhancement of Solubility and Dissolution Rate of Poorly Aqueous Soluble Drug Simvastatin: In vitro–In vivo Evaluation

A number of synthesized chemical molecules suffer from low aqueous solubility problems. Enhancement of aqueous solubility, dissolution rate, and bioavailability of drug is a very challenging task in drug development. In the present study, solubility and dissolution of poorly aqueous soluble drug simvastatin (SIM) was enhanced using hydrophilic, low viscosity grade polymer hydroxypropyl methylcellulose (HPMC K₃LV). The co-solvent evaporation method was developed for efficient encapsulation of hydrophobic drug in polymer micelles of HPMC K₃LV. Spray drying and rotaevaporation method were applied for solvent evaporation. Co-solvent-evaporated mixture in solid state was determined by differential scanning calorimetry (DSC), X-ray diffraction studies (XRD), scanning electron microscopy, and Fourier-transform infrared spectroscopy. In vitro–in vivo studies were performed on co-solvent-evaporated mixture and compared with SIM. In vivo study was conducted on healthy albino rats (Wister strain), and formulations were administered by oral route. Results of the study show the conversion of crystalline form of SIM into amorphous form. The dissolution rate was remarkably increased in co-solvent-evaporated mixtures compared to SIM. co-solvent-evaporated mixtures showed better reduction in total cholesterol and triglyceride levels than the SIM. The low-viscosity grade HPMC acts as a surfactant, which enhances the wetting of drug and thus improves the solubility of drug. The co-solvent evaporation method provides good encapsulation efficiency and produces amorphous form of SIM, which gave better solubility and dissolution than the crystalline SIM.     

Use of Polyvinyl Alcohol as a Solubility-Enhancing Polymer for Poorly Water Soluble Drug Delivery (Part 1)

Polyvinyl alcohol (PVAL) has not been investigated in a binary formulation as a concentration-enhancing polymer owing to its high melting point/high viscosity and poor organic solubility. Due to the unique attributes of the KinetiSol® dispersing (KSD) technology, PVAL has been enabled for this application and it is the aim of this paper to investigate various grades for improvement of the solubility and bioavailability of poorly water soluble active pharmaceutical ingredients. Solid amorphous dispersions were created with the model drug, itraconazole (ITZ), at a selected drug loading of 20%. Polymer grades were chosen with variation in molecular weight and degree of hydroxylation to determine the effects on performance. Differential scanning calorimetry, powder X-ray diffraction, polarized light microscopy, size exclusion chromatography, and dissolution testing were used to characterize the amorphous dispersions. An in vivo pharmacokinetic study in rats was also conducted to compare the selected formulation to current market formulations of ITZ. The 4-88 grade of PVAL was determined to be effective at enhancing solubility and bioavailability of itraconazole.     

Effervescence Assisted Fusion Technique to Enhance the Solubility of Drugs

The solubility of five poorly soluble drugs was enhanced by using an effervescence assisted solid dispersion (EASD) technique. EASDs were prepared by using modified fusion method. Drug and hydrophilic carrier were melted, and in this molten mixture, effervescence was generated by adding effervescence couple comprising organic acid (citric acid) and carbonic base (sodium bicarbonate). Solubility of drug powders, solid dispersions, and EASDs was determined at 25°C using shake flask method. Atorvastatin calcium, cefuroxime axetil, clotrimazole, ketoconazole, and metronidazole benzoate were estimated using a spectrophotometer at 246, 280, 260, 230, and 232 nm (λ_max), respectively. Solubility of atorvastatin calcium (from 100 to 345 μg/ml), cefuroxime axetil (from 441 to 1948 μg/ml), clotrimazole (from 63 to 677 μg/ml), ketoconazole (from 16 to 500 μg/ml), and metronidazole benzoate (from 112 to 208 μg/ml) in EASDs was enhanced by 3.45-, 4.4-, 10.7-, 31.2-, and 1.8-fold, respectively. Scanning electron micrographs of drug powder, solid dispersion, and EASDs were compared. Scanning electron micrographs of EASDs showed a uniform distribution of drug particles in the carrier matrix. Morphology (size and shape) of cefuroxime axetil particles was altered in solid dispersion as well as in EASD. EASDs showed better solubility enhancement than conventional solid dispersions. The present technique is better suitable for drugs having a low melting point or melt without charring. Effervescence assisted fusion technique of preparing solid dispersions can be employed for enhancing solubility, dissolution, and bioavailability of poorly soluble drugs.KEY WORDS: dissolution, effervescence, fusion, solid dispersion, solubility     

Dissolution Enhancement of a Drug Exhibiting Thermal and Acidic Decomposition Characteristics by Fusion Processing: A Comparative Study of Hot Melt Extrusion and KinetiSol® Dispersing

In this study, hot melt extrusion (HME) and KinetiSol® Dispersing (KSD) were utilized to prepare dissolution-enhanced solid dispersions of Roche Research Compound A (ROA), a BCS class II drug. Preformulation characterization studies showed that ROA was chemically unstable at elevated temperatures and acidic pH values. Eudragit® L100-55 and AQOAT® LF (HPMCAS) were evaluated as carrier polymers. Dispersions were characterized for ROA recovery, crystallinity, homogeneity, and non-sink dissolution. Eudragit® L100-55 dispersions prepared by HME required the use of micronized ROA and reduced residence times in order to become substantially amorphous. Compositions containing HPMCAS were also prepared by HME, but an amorphous dispersion could not be obtained. All HME compositions contained ROA-related impurities. KSD was investigated as a method to reduce the decomposition of ROA while rendering compositions amorphous. Substantially amorphous, plasticizer free compositions were processed successfully by KSD with significantly higher ROA recovery values and amorphous character than those achieved by HME. A near-infrared chemical imaging analysis was conducted on the solid dispersions as a measure of homogeneity. A statistical analysis showed similar levels of homogeneity in compositions containing Eudragit® L100-55, while differences were observed in those containing HMPCAS. Non-sink dissolution analysis of all compositions showed rapid supersaturation after pH adjustment to approximately two to three times the equilibrium solubility of ROA, which was maintained for at least 24 h. The results of the study demonstrated that KSD is an effective method of forming dissolution-enhanced amorphous solid solutions in cases where HME is not a feasible technique.     

New Nanometric Solid Dispersions of Glibenclamide in Neusilin<Superscript>®</Superscript> UFL2

To improve the poor water solubility and dissolution rate of the oral hypoglycemic drug glibenclamide, it was molecularly dispersed in Neusilin^® UFL2, an amorphous synthetic form of magnesium aluminometasilicate, at different proportions; the physicochemical and biopharmaceutical properties, as well as the stability of the four different batches recovered were characterised, and it was determined that complete dispersion of glibenclamide in the amorphous polymer was obtained at the drug to Neusilin ratio of 1 to 2.5. Completely amorphous dispersion was proven by Thermal Analysis and X-Ray Powder Diffractometry. Very small particles were obtained, ranging from approximately 200 to 400 nm. The amorphous batches were physically and chemically stable for the entire duration of experiments. The physicochemical properties of the four batches were compared to those of the starting materials and physical mixtures of Neusilin^® UFL2 and glibenclamide, the latter showing the typical behaviour of simple mixes, i.e., the additivity of properties of single components. The dissolution studies of the four solid dispersions revealed a very high dissolution rate of the completely amorphous batches (Batches 3 and 4), behaviour that was ascribed to their high Intrinsic dissolution rate due to the amorphous characteristics of the solid dispersions, to their very small particle size, and to the presence of polysorbate 80 that improved solid wettability. The technique under investigation thus proved effective for recovering stable amorphous dispersions of very small particle sizes.     

Solubility Enhancement of Lovastatin by Modified Locust Bean Gum Using Solid Dispersion Techniques

The aim of the present study was to improve the solubility of poorly water soluble drug lovastatin (LS) by solid dispersion (SD) techniques using modified locust bean gum (MLBG) as a carrier. The locust bean gum (LBG) was modified by heating and there observed irreversible decrease in viscosity, whereas swelling property remains unaffected. The advantage of modification of LBG was illustrated by difference in dissolution profiles of their SD. Effect of polymer concentration and methods of preparation on solubility enhancement were studied using solubility and dissolution studies, respectively. The result of solubility study showed increase in solubility of LS with increase in concentration of MLBG. It was found that the dissolution rate of LS from its SD was dependent on the method of preparation of solid dispersions. Dissolution study revealed that the modified solvent evaporation is most convenient and effective method for solubility enhancement of poorly water soluble drug LS, among various methods of preparation of SD. The prepared SDs were characterized by differential scanning calorimetry, scanning electron microscopy, and X-ray diffraction study. In vivo study was performed by measuring 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG Co-A) reductase inhibition activity. Significant reduction in HMG Co-A reductase activity was observed in case of solid dispersions of LS than plain LS. In conclusion, MLBG could be used as a potential carrier in enhancing the dissolution rate and bioavailability of LS.     

Stability-enhanced Hot-melt Extruded Amorphous Solid Dispersions via Combinations of Soluplus? and HPMCAS-HF

The aim of this study was to evaluate a novel combination of Soluplus® and hypromellose acetate succinate (HPMCAS-HF) polymers for solubility enhancement as well as enhanced physicochemical stability of the produced amorphous solid dispersions. This was accomplished by converting the poorly water-soluble crystalline form of carbamazepine into a more soluble amorphous form within the polymeric blends. Carbamazepine (CBZ), a Biopharmaceutics Classification System class II active pharmaceutical ingredient (API) with multiple polymorphs, was utilized as a model drug. Hot-melt extrusion (HME) processing was used to prepare solid dispersions utilizing blends of polymers. Drug loading showed a significant effect on the dissolution rate of CBZ in all of the tested ratios of Soluplus® and HPMCAS-HF. CBZ was completely miscible in the polymeric blends of Soluplus® and HPMCAS-HF up to 40% drug loading. The extrudates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and dissolution studies. DSC and XRD data confirmed the formation of amorphous solid dispersions of CBZ in the polymeric blends of Soluplus® and HPMCAS-HF. Drug loading and release of CBZ was increased with Soluplus® (when used as the primary matrix polymer) when formulations contained Soluplus® with 7–21% (w/w) HPMCAS-HF. In addition, this blend of polymers was found to be physically and chemically stable at 40°C, 75% RH over 12 months without any dissolution rate changes.KEY WORDS: carbamazepine, hot-melt extrusion, HPMCAS-HF, Soluplus®, stability     

Expanding the Application and Formulation Space of Amorphous Solid Dispersions with KinetiSol®: a Review

Due to the high number of poorly soluble drugs in the development pipeline, novel processes for delivery of these challenging molecules are increasingly in demand. One such emerging method is KinetiSol, which utilizes high shear to produce amorphous solid dispersions. The process has been shown to be amenable to difficult to process active pharmaceutical ingredients with high melting points, poor organic solubility, or sensitivity to heat degradation. Additionally, the process enables classes of polymers not conventionally processable due to their high molecular weight and/or poor organic solubility. Beyond these advantages, the KinetiSol process shows promise with other applications, such as the production of amorphous mucoadhesive dispersions for delivery of compounds that would also benefit from permeability enhancement.     

Wetting Kinetics: an Alternative Approach Towards Understanding the Enhanced Dissolution Rate for Amorphous Solid Dispersion of a Poorly Soluble Drug

Developing amorphous solid dispersions of water-insoluble molecules using polymeric materials is a well-defined approach to improve the dissolution rate and bioavailability. While the selected polymer plays a vital role in stabilizing the amorphous solid dispersion physically, it is equally important to improve the dissolution profile by inhibiting crystallization from the supersaturated solution generated by dissolution of the amorphous material. Furthermore, understanding the mechanism of dissolution rate enhancement is of vital importance. In this work, wetting kinetics was taken up as an alternative approach for understanding the enhanced dissolution rate for amorphous solid dispersion of a poorly soluble drug. While cilostazol (CIL) was selected as the model drug, povidone (PVP), copovidone, and hypromellose (HPMC) were the polymers of choice. The concentrations against time profiles were evaluated for the supersaturated solutions of CIL in the presence and absence of the selected polymers. The degree of supersaturation increased significantly with increase in polymer content within the solid dispersion. While povidone was found to maintain the highest level of supersaturation for the greatest length of time both in dissolution and solution crystallization experiments, copovidone and hypromellose were found to be the less effective as crystallization inhibitor. The ability of polymers to generate and maintain supersaturated drug solutions was assessed by dissolution studies. The wetting kinetics was compared against the solid dispersion composition to establish a correlation with enhanced dissolution rate.KEY WORDS: Cilostazol, Crystallization inhibition, Solid dispersions, Supersaturated solutions, Wetting kinetics     

Modulating Drug Release and Enhancing the Oral Bioavailability of Torcetrapib with Solid Lipid Dispersion Formulations

The development of drug dispersions using solid lipids is a novel formulation strategy that can help address the challenges of poor drug solubility and systemic exposure after oral administration. The highly lipophilic and poorly water-soluble drug torcetrapib could be effectively formulated into solid lipid microparticles (SLMs) using an anti-solvent precipitation strategy. Acoustic milling was subsequently used to obtain solid lipid nanoparticles (SLNs). Torcetrapib was successfully incorporated into the lipid matrix in an amorphous state. Spherical SLMs with mean particle size of approximately 15–18 μm were produced with high drug encapsulation efficiency (>96%) while SLNs were produced with a mean particle size of 155 nm and excellent colloidal stability. The in vitro drug release and the in vivo absorption of the solid lipid micro- and nanoparticles after oral dosing in rats were evaluated against conventional crystalline drug powders as well as a spray dried amorphous polymer dispersion formulation. Interestingly, the in vitro drug release rate from the lipid particles could be tuned for immediate or extended release by controlling either the particle size or the precipitation temperature used when forming the drug-lipid particles. This change in the rate of drug release was manifested in vivo with changes in Tmax as well. In addition, in vivo pharmacokinetic studies revealed a significant increase (∼6 to 11-fold) in oral bioavailability in rats dosed with the SLMs and SLNs compared to conventional drug powders. Importantly, this formulation approach can be performed rapidly on a small scale, making it ideal as a formulation technology for use early in the drug discovery timeframe.Electronic supplementary materialThe online version of this article (doi:10.1208/s12249-015-0299-8) contains supplementary material, which is available to authorized users.KEY WORDS: anti-solvent precipitation, controlled release, formulation, nanoparticles, solid lipid     

Low-Viscosity Hydroxypropylcellulose (HPC) Grades SL and SSL: Versatile Pharmaceutical Polymers for Dissolution Enhancement, Controlled Release, and Pharmaceutical Processing

Hydroxypropylcellulose (HPC)-SL and -SSL, low-viscosity hydroxypropylcellulose polymers, are versatile pharmaceutical excipients. The utility of HPC polymers was assessed for both dissolution enhancement and sustained release of pharmaceutical drugs using various processing techniques. The BCS class II drugs carbamazepine (CBZ), hydrochlorthiazide, and phenytoin (PHT) were hot melt mixed (HMM) with various polymers. PHT formulations produced by solvent evaporation (SE) and ball milling (BM) were prepared using HPC-SSL. HMM formulations of BCS class I chlorpheniramine maleate (CPM) were prepared using HPC-SL and -SSL. These solid dispersions (SDs) manufactured using different processes were evaluated for amorphous transformation and dissolution characteristics. Drug degradation because of HMM processing was also assessed. Amorphous conversion using HMM could be achieved only for relatively low-melting CBZ and CPM. SE and BM did not produce amorphous SDs of PHT using HPC-SSL. Chemical stability of all the drugs was maintained using HPC during the HMM process. Dissolution enhancement was observed in HPC-based HMMs and compared well to other polymers. The dissolution enhancement of PHT was in the order of SE > BM > HMM > physical mixtures, as compared to the pure drug, perhaps due to more intimate mixing that occurred during SE and BM than in HMM. Dissolution of CPM could be significantly sustained in simulated gastric and intestinal fluids using HPC polymers. These studies revealed that low-viscosity HPC-SL and -SSL can be employed to produce chemically stable SDs of poorly as well as highly water-soluble drugs using various pharmaceutical processes in order to control drug dissolution.KEY WORDS: controlled release formulations, hydroxypropylcellulose, melt extrusion, solid dispersion