Preparation and in vitro/in vivo evaluation of sustained-release metformin hydrochloride pellets.

In this study, metformin hydrochloride (MH) sustained-release pellets were successfully prepared by centrifugal granulation. Seed cores preparation, drug layering, talc modification and coating of polymeric suspensions were carried out in a centrifugal granulator. Talc modification was performed before coating in order to overcome the high water solubility of metformin. The influence of surface modification by talc, the effects of Eudragit types and ratios, as well as the correlation between in vitro release and in vivo absorption were investigated in detail. Experimental results indicated that talc modification made a decisive contribution to controlling the drug release by avoiding drug dumping. Three dissolution media: 0.1 M HCl, distilled water and pH 6.8 phosphate buffer were employed to determine the in vitro release behaviors of the above metformin hydrochloride pellets. The relative bioavailability of the sustained-release pellets was studied in 12 healthy volunteers after oral administration in a fast state using a commercially available immediate release tablet (Glucophage) as a reference. Following coating with a blend of Eudragit L30D-55 and Eudragit NE30D (1:20), at 7% or 10% coating level, respectively (referred to as F-2, F-3), the pellets acquired perfect sustained-release properties and good relative bioavailability. The Cmax, Tmax and relative bioavailability for F-2 and F-3 coated pellets were 1.21 microg/ml, 6 h, 97.6% and 1.65 microg/ml, 8 h, 165%, respectively. Combined use of two Eudragit polymers with different features as coating materials produced the desired results. Restricted delivery of metformin hydrochloride to the small intestine from differently coated pellets resulted in increased relative bioavailability and a sustained release effect. The adoption of several different pH dissolution media established a better relationship between the in vitro release and in vivo absorption of the sustained-release pellets.     

Relative bioavailability of enteric coated pellets, stearate and ethylsuccinate formulations of erythromycin

In a randomized three-phase crossover study, 12 healthy male volunteers were given three 12-hourly 500-mg doses of erythromycin base, as enteric coated pellets in capsules (2 X 250 mg), erythromycin stearate tablet (1 X 500 mg), or erythromycin ethylsuccinate sachet (1 X 500 mg). The reaction time after administration of the pellets is significantly longer than after the stearate or ethylsuccinate formulations. The peak serum concentrations are higher for the pellets after both the 1st and 3rd dose. The time to reach peak concentrations is significantly longer for the pellets than for the stearate and ethylsuccinate formulations. The area under the serum concentration/time curve during 0-8 h after both doses is highest for the pellets. In conclusion, these findings indicate that despite the longer lag (1.8-1.2 h), the extent of gastrointestinal absorption and bioavailability of erythromycin is apparently greater for the base pellets than for the stearate and ethylsuccinate formulations.     

挤出滚圆-流化床包衣法制备决明子微丸的研究

目的考察并优化挤出滚圆-流化床包衣法制备决明子醇提物微丸的工艺条件。方法采用L9（34）正交设计实验优化制剂工艺条件制备决明子醇提物微丸,考察微丸的粉体学性质,流化制粒包衣机将微丸包衣,并测定体外溶出度。结果以MCC为主要辅料,载药量40%,挤出频率30 Hz,滚圆频率50 Hz,滚圆时间4 min,经流化床包衣制得的决明子醇提物微丸,圆整度、流动性、体外释放度均较理想。结论应用挤出滚圆-流化床包衣法制备决明子醇提物微丸,其工艺简便,成品质量好。     

In vitro dissolution and in vivo oral absorption of methylphenidate from a bimodal release formulation in healthy volunteers

PURPOSE: The objective of this study was to evaluate the in vitro dissolution and in vivo absorption of D,L-threo-methylphenidate (MPH) from a novel bimodal release formulation (Ritalin LA capsule) compared with an immediate-release formulation (Ritalin IR tablet) in healthy volunteers. METHODS: The bimodal release formulation contains 50% of the dose in the immediate-release (IR) beads and 50% in polymethacrylate-coated, delayed-release (DR) beads. To better understand the impact of dissolution from the DR beads on oral absorption of MPH, three Ritalin LA formulations with different dissolution profiles for the DR beads (referred to as slow-, medium and fast-release formulations) were prepared, and tested together with the immediate-release formulation in 18 healthy male and female volunteers after a single oral dose under fasted conditions. The rate and extent of oral absorption of MPH were evaluated based on the overall Cmax, tmax and AUC values, as well as the Cmax, tmax and AUC values for each individual peak of the bimodal plasma concentration-time profile. The in vivo absorption-time profile was also examined by deconvolution. RESULTS: All three Ritalin LA formulations demonstrated similar bimodal plasma concentration-time profiles with two peak concentrations observed at approximately 2 and approximately 6 h post dose, mimicking that of Ritalin IR tablets given 4 h apart. Deconvolution results showed that the absorption of MPH was biphasic, with a rapid absorption phase between 0 to approximately 2 h, and a somewhat slower second absorption between approximately 3-6 h, consistent with the in vitro bimodal release characteristics of Ritalin LA formulation. The three Ritalin LA formulations were bioequivalent to one another based on the overall Cmax and AUC values and the corresponding values describing the first and second peaks, although their in vitro dissolution profiles for the DR beads were different. Compared with Ritalin IR, the Ritalin LA formulation demonstrated a similar rate of absorption for the first peak, a lower second Cmax and a higher trough concentration between peaks, as well as similar overall plasma AUC. CONCLUSIONS: Following a single oral drug administration, Ritalin LA demonstrated a two-peak plasma concentration-time profile, similar to that of the IR formulation given 4 h apart, but with less fluctuation in the plasma concentration-time profile. The in vivo biphasic absorption of MPH appeared to be well correlated with the bimodal dissolution characteristics of this new Ritalin LA formulation, and some changes in the dissolution profiles for the DR beads appeared not to affect the overall bioavailability of MPH in humans.     

In-vitro and in-vivo studies of pectin/ethylcellulosefilm-coated pellets of 5-fluorouracil for colonic targeting

The aim of the present study was to define in-vitro and in-vivo characteristics of pectin/ethylcellulose-film-coated pellets of 5-fluorouracil (5-FU) for colonic targeting. The pellet cores were coated to different film thicknesses with three different pectin/ethylcellulose formulations using a fluidized bed coater. The gastrointestinal (GI) transit of coated pellets was determined by counting the percentage of coated pellets in the GI lumen by celiotomy at certain times after oral administration. 5FU was administered to rats at a dose of 15 mg kg(-1). The toxicity of 5-FU in the GI tract was evaluated using histological examination. The 1:2 ratio pectin:ethylcellulose-coated pellets with 30% total weight gain (TWG-30%) produced more satisfactory drug-release profiles in the simulated gastric, intestinal and colonic fluids. Most of the coated pellets were eliminated from the stomach in 2 h, moved into the small intestine after 2-4 h, and reached the large intestine after 4 h. After oral administration of coated pellets, 5-FU started appearing in the plasma at 7 h, and reached peak plasma concentration (Cmax) of 3.21+/-2.01 microg mL(-1) at 16 h (Tmax); the Cmax for uncoated pellets was 22.21+/-2.60 microg mL(-1) at Tmax 0.75 h. The TWG-30% formulation showed delayed Tmax, decreased Cmax and prolonged mean residence time compared with uncoated pellets. Marked pathological features in the colon were seen in rats given coated pellets, but no injuries were observed in the upper GI tract. The formulation of TWG-30% could deliver 5-FU to the colon for local action.     

pH-dependent release of platycodin mitigates its gastrointestinal mucosa irritation after oral administration in rats

The present study aimed to evaluate the gastrointestinal mucosa irritation of three platycodin formulations. Platycodin-loaded core pellets were prepared via extrusion–spheronization method and coated with Eudragit^® L100-55 (L100) or Eudragit^® S100 (S100) for pH-dependent release. The release of platycodin D from coated pellets exhibited pH dependent release profiles. The pharmacokinetic study in rats showed that T_max of the coated pellets were prolonged as compared to that of un-coated pellets. The S100-coated pellets possess a lower C_max and decreased AUC_0–24h as compared to the L100-coated and uncoated pellets. Hematoxylin-eosin staining and nuclear factor Kappa B (NF-κB) measurement were carried out to observe the gastrointestinal mucosa irritations. The results revealed that the irritations of platycodin on the upper gastrointestinal mucosa are dose-dependent. However, no obvious irritation effect on the gastrointestinal tissues of rats was detected after oral administration of the coated pellets. In addition, the amount of NF-κB in the stomach of rats treated with the uncoated pellets was about fivefold higher as compared to that of the coated pellets. In summary, the L100-coated platycodin pellets exhibited higher oral bioavailability and less gastrointestinal mucosa irritations as compared to the other two formulations.     

Chitosan/Kollicoat SR 30D film-coated pellets of aminosalicylates for colonic drug delivery

The purpose of the study was to (i) prepare the chitosan/Kollicoat SR 30D film-coated pellets for colonic drug delivery, and (ii) evaluate the colonic delivery and efficacy of these coated pellets in the rat. The pellets were coated to different film thickness with chitosan/Kollicoat SR 30D formulations. In vitro drug release was assessed in simulated gastrointestinal (GI) tract conditions. Biodistribution of aminosalicylates (5-ASA) in GI tract and plasma was measured after oral administration of coated or uncoated 5-ASA pellets. Efficacy of the coated or uncoated 5-ASA pellets was tested in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rat colitis model. Healing of induced colitis was assessed by measuring the myeloperoxidase activities, colon wet weight/body weight, and damage score. The coating was susceptible to bacteria digestion, resulting in an increase in the release of 5-ASA from the coated pellets. After administration of the coated pellets, the drug concentration in the large intestine was higher than those of uncoated pellets. In plasma, the observed mean C_max from the coated pellets was significantly lower than that of the uncoated pellets. Chitosan/Kollicoat SR 30D film-coated pellets could deliver the 5-ASA to the targeted site, providing effective treatment for inflammatory bowel disease. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:186–195, 2010     

Comparison of the dissolution and pharmacokinetic profiles of two galenical formulations of the endothelin receptor antagonist macitentan

Macitentan (ACT-064992) is an orally active endothelin receptor antagonist. We first compared the in vitro dissolution characteristics of uncoated and film-coated tablets with hard gelatin capsules containing 10 mg ACT-064992. Subsequently, we compared the oral pharmacokinetics of ACT-064992 and its active metabolite ACT-132577 of the coated tablet and the gelatin capsule formulation in 11 male volunteers.The dissolution profile showed a rapid disintegration of all formulations with >90% dissolution of ACT-064992 within 45 min. The pharmacokinetics of ACT-064992 and its metabolite ACT-132577 were comparable for the two formulations. ACT-064992 revealed a slow absorption (median t_max 8 h) and a terminal half-life of approximately 13 h. Bioequivalence criteria were met for AUC_0−t and AUC_0−∞. Mean C_max was 19% lower after ingestion of the tablet compared to capsules with its lower 90% confidence limit below the accepted bioequivalence range. The pharmacokinetics of the metabolite ACT-132577, characterized by a t_max of approximately 48 h and a terminal half-life of approximately 45 h, was not different between the two formulations.We conclude that the absorption profile of the tablet differs from the capsule in peak but not in total exposure, which is not expected to be of clinical significance.     

Development and in Vitro-in Vivo Evaluation of a Multiparticulate Sustained Release Formulation of Diltiazem

Purpose. To develop and evaluate the in vitro/in vivo performance of diltiazem sustained release pellets that were prepared by the Wurster column process. Methods. Pellets containing diltiazem were prepared by spraying a slurry of micronized diltiazem hydrochloride, pharmaceutical glaze and alcohol onto an appropriate mesh fraction of nonpareil seeds using the Wurster column. A two-step drug layering process was used to increase drug loading from 60% to 75%. The oven-dried diltiazem basic pellets were coated with eth-ylcellulose/dibutyl sebacate coating solution to yield diltiazem sustained release pellets. An open, randomized Latin square, three-way crossover clinical study was used to evaluate the in vivo performance of the coated product. Results. Altering the mesh fraction of the starting nonpareil seeds for this layering process was found to affect the release characteristics of drug from the pellets. An oven-drying step was required to stabilize the diltiazem basic pellets. The thicker the drug loading layer the longer the oven drying is needed to stabilize the pellets. The diltiazem sustained release pellets produced by these methods displayed sustained release dissolution profiles both in vitro and in vivo. Diltiazem basic pellets coated with a 0.6% ethylcellulose/dibutyl sebacate coating showed a different rate of absorption (lower C _max and higherT _max) and the same extent of absorption as compared to Cardizem^® tablets. Conclusions. Clinical data confirmed that this formulation approach is an effective means to produce a diltiazem sustained release product.     

进口与国产利培酮薄膜衣片在健康志愿者的生物等效性

目的 研究利培酮薄膜衣片(抗精神分裂症药)在健康志愿者的药代动力学和生物等效性.方法 23名健康男性志愿者随机交叉、单剂量口服受试制剂(进口)和参比制剂(国产)2 mg后,用HPLC-MS/MS测定血浆中利培酮及9-羟基利培酮浓度,计算主要药代动力学参数,评价2种制剂的生物等效性.结果 受试制剂和参比制剂的主要药代动力学参数,利培酮:AUC0～t分别为(94.76±82.93)和(103.05±117.71)ng·h·mL-1;AUC0～1分别为(96.72±84.52)和(105.19±119.36)ng·h·mL0-1;Cmax分别为(15.91±5.63)和(16.21±11.56)ng·mL-1;tmax分别为(1.14±0.73)和(1.15±0.54)h;t1/2分别为(7.32±5.94)和(7.44±6.50)h,受试制剂的相对生物利用度为(106.68±40.21)%.9-羟基利培酮:AUC0-96h分别为(268.56±85.20)和(279.64 ±117.86)ng·h·mL-1;AUC0-∞分别为(282.74±87.46)和(294.28±120.32)ng·h·mL-1;Cmax分别为(10.84±4.69)和(11.11±4.80)ng·mL-1;tmax分别为(3.35±2.32)和(4.48±2.76)h;t1/2分别为(23.18±3.26)和(23.12±4.31)h,受试制剂的相对生物利用度为(101.37±27.23)%.结论 2种制剂具有生物等效性.     

Bioavailability of ibuprofen from hot-melt extruded mini-matrices

The bioavailability of ibuprofen from hot-melt extruded mini-matrices based on ethyl cellulose and a hydrophilic excipient was tested. During the in vivo evaluation an oral dose of 300 mg ibuprofen was administered to healthy volunteers (n = 9) in a randomized cross-over study and compared with a commercially available sustained release product (Ibu-slow). The plasma samples were analysed by a validated HPLC-UV method. One mini-matrix formulation (F-1) consisted of 30% ibuprofen, 35% ethyl cellulose and 35% hydroxypropyl methylcellulose (Metolose 60 SH 50), while the second formulation (F-2) contained 60% ibuprofen, 20% ethyl cellulose and 20% xanthan gum. These mini-matrices were administered in hard gelatine capsules. Both formulations behaved in vivo as sustained release formulations with an HVD(t50% Cmax) value (time span during which the plasma concentration is at least 50% of the Cmax value) of 7.6 and 12.0 h for formulations F-1 and F-2, respectively, whereas a value of 5.2 h was obtained for Ibu-slow. Although a significantly higher Cmax and AUC(0-24 h) was seen for the reference product, the relative bioavailability of both experimental formulations was about 80%.     

Starch-based coatings for colon-specific delivery. Part II: Physicochemical properties and in vitro drug release from high amylose maize starch films

This work reports an investigation into free-film properties of a high amylose maize starch-based film coating that has been used in the preparation of formulations for drug delivery to the colon (WO 2008/012573 A1) and relates these properties to in vitro drug release from pellets.Maize starch/ethylcellulose free films were prepared and characterised by scanning electron microscopy (SEM), light microscopy, modulated differential scanning calorimetry (mDSC), Fourier-transform infrared (FT-IR), X-ray and % swelling in aqueous fluids with pH conditions similar to the stomach and small intestine. 5-ASA release from film-coated pellets was tested in enzyme free simulated gastric fluid and phosphate buffer pH 7.2. Selected formulations were further assessed in simulated gastric and intestinal fluids containing pepsin and pancreatin, respectively.The free films prepared were smooth and homogeneous in their appearance. The two polymers are immiscible, and neither mDSC nor FT-IR could detect interactions between them. Films made from high amylose starches were found to have a considerably lower swelling ability than high amylopectin-based films, and they suppressed drug release in the enzyme free media successfully.5-ASA release from pellets coated with mixtures of high amylose starches (Hylon^® VII, Hylon^® V or LAPS) and Surelease^® in a ratio of 1 to 2 w/w was found to be minimal in simulated gastric and intestinal fluids. This suggests that these mixed films provide starch domains that are resistant to the enzymes present in the upper GI tract and thus can potentially be used in the preparation of colon-specific delivery devices. Starches with a minimum amylose content of 56% such as the starches used in this study (Hylon^® VII and Hylon^® V) are preferred, and although pure amylose can also be used this is not essential.     

A new formulation of controlled release amitriptyline pellets and its in vivo/in vitro assessments

Controlled-release amitriptyline pellets (ATP) were formulated and its oral bioavailability was assessed in human volunteers after oral administration under fasting conditions. Core pellets were prepared using a CF granulator by two different methods (powder layering and solvent spraying) and coated with Eudragit RS or RL 100. Physical characteristics and dissolution rates of core pellets and coated pellets were evaluated to optimize the formulation. Powder layering method resulted in a better surface morphology than solvent spraying method. However, physical properties of the products were poorer when prepared by powder layering method with respect to hardness, friability and density. The dissolution profile of amitriptyline coated with Eudragit RS 100 was comparable to that of commercially available amitriptyline enteric-coated pellets (Saroten retard). After the oral administration of both products at the dose of 50 mg, the mean maximum concentrations (Cmax) were 36.4 and 29.7 ng/mL, and the mean areas under the concentration-time curve (AUC(0-96)) were 1180.2 and 1010.7 ng.h/mL for ATP and Saroten retard, respectively. The time to reach the maximum concentrations (Tmax) was 6 h for both formulations. Statistical evaluation suggested that ATP was bioequivalent to Saroten retard.     

Gastrointestinal transit and release of 5-aminosalicylic acid from 153Sm-labelled mesalazine pellets vs. tablets in male healthy volunteers

BACKGROUND: Mesalazine (5-aminosalicylic acid)-containing formulations, designed to optimize drug delivery to the ileo-caecal region, represent a cornerstone in the treatment of inflammatory bowel diseases. AIM: : To test, by means of pharmaco-scintigraphy, whether novel mesalazine-containing pellets release 5-aminosalicylic acid in the same target region as mesalazine tablets (Salofalk). METHODS: Fourteen healthy male volunteers received a single dose of either pellets or tablets containing 500 mg of mesalazine and 2 mg of 152Sm2O3 with a 1-week washout period. The gastrointestinal transit of 153Sm, incorporated into the formulations, was followed by gamma-scintigraphy. Mesalazine release was verified by assessing 5-aminosalicylic acid plasma pharmacokinetics. RESULTS: The formulations reached the ileo-caecal target region almost at the same time (3.3 +/- 1 and 3.8 +/- 1 h for pellets and tablets, respectively). Plasma 5-aminosalicylic acid tmax values were comparable and corresponded to the time during which the formulations were located in the target region. Plasma AUC values were significantly lower for pellets, which might be explained by a more prolonged release of 5-aminosalicylic acid. CONCLUSIONS: Novel mesalazine pellets and Salofalk tablets release active 5-aminosalicylic acid in the same target region and pass through the gastrointestinal tract under fasting conditions in healthy volunteers in a comparable time. From a comparison of in vitro dissolution and plasma concentration data, a slower and more prolonged release of 5-aminosalicylic acid from pellets is suggested.     

The use of formulation technology to assess regional gastrointestinal drug absorption in humans.

The aim of this study was to assess the feasibility of using oral modified-release formulations for the purposes of site-specific targeting and regional drug absorption assessment in man. An immediate release pellet formulation containing ranitidine as the model drug of choice for the study was fabricated by extrusion-spheronisation, and then film coated with either the enteric polymer polyvinyl acetate phthalate or the bacteria-degradable polymer amylose, in combination with ethylcellulose, to effect drug release within the small intestine and colon, respectively. Optimised formulations were evaluated in vivo in ten healthy volunteers, who each received, on four separate occasions, the immediate release, small intestinal release and colonic release formulations (each equivalent to 150mg ranitidine), and an intravenous injection of ranitidine (equivalent to 50mg ranitidine). Blood samples were collected and assessed for ranitidine concentration, and radiolabelled placebo pellets were co-administered with the coated ranitidine pellets to monitor their gastrointestinal transit using a gamma camera. Ranitidine was rapidly released and absorbed from the immediate release formulation, whereas the enteric formulation (10% coat weight gain) delayed drug release until some or all of the pellets had emptied into the small intestine. The amylose-ethylcellulose coated formulation (coat ratio 1:3, coat weight gain 25%) retarded ranitidine release until the pellets had reached the colon. The mean absolute bioavailability of ranitidine from the immediate release, small intestinal release and colonic release formulations were 50.6, 46.1 and 5.5%, respectively. These data are in general agreement to those obtained from a previous regional intubation study. The present study therefore demonstrates the practical potential of utilising a non-invasive, formulation-based approach to assess drug absorption from different regions of the human gastrointestinal tract.     

陈香露白露薄膜衣片的研制

目的:制备陈香露白露薄膜衣片,提高药物稳定性。方法:选用不同的粘合剂制备片芯,再选用不同的包衣材料进行包衣,比较陈香露白露薄膜衣片与糖衣片的稳定性。结果:采用10%聚乙烯吡咯烷酮乙醇液为粘合剂制备片芯,用隔离材料玉米阮将片芯保护,采用上海卡乐康公司的黄色或红棕色胃溶性包衣粉制备的陈香露白露薄膜衣片在外观质量上优于其它材料制备的成品,尤其是防渗油和防潮性方面优势明显;薄膜衣片稳定性优于糖衣片。结论:陈香露白露薄膜衣片质量稳定,制备工艺简单。     

Egg albumin microspheres containing paracetamol for oral administration. II. In vivo investigation

Egg albumin microspheres containing paracetamol for oral administration were prepared and their in vivo characteristics evaluated. The egg albumin microspheres were able to improve the organoleptic characteristics of paracetamol formulations. The pharmacokinetic characteristics of three different formulations of paracetamol were evaluated in six volunteers. The formulations administered orally were: (1) Paracetamol granulated with lactose (reference), (2) Egg albumin microspheres and (3) Egg albumin microspheres coated with polymethacrylate. The pharmacokinetic characteristics for formulations 1 and 2 were similar but formulation 3 gave significant differences (p less than 0.05) in Ka, Cmax and tmax. No significant differences in relative bioavailability were observed.     

Comparative target site pharmacokinetics of immediate- and modified-release formulations of cefaclor in humans

Optimal dosing of beta-lactam antibiotics aims at maximizing the time at which drug levels in the interstitial space fluid (ISF)--the fluid that surrounds the causative microorganisms at the target site--exceed the minimal inhibitory concentration (MIC). One potentially attractive strategy to achieve this goal is to administer antibiotics as oral sustained-release formulations. The present study was designed to test the hypothesis that sustained-release formulations could lead to a more suitable pharmacokinetic profile in the ISF at the relevant target site. For this purpose, time versus cefaclor concentration profiles attained in the ISF were measured following administration of two formulations, an immediate- (500 mg IR) and a modified-release formulation in two different doses (500 mg MR and 750 mgMR) in a three-way crossover study of healthy male volunteers (n = 12). For the measurement of unbound cefaclor concentrations in the ISF of human skeletal muscle, the in vivo microdialysis technique was employed. For all three formulations, unbound cefaclor concentration in the ISF closely followed individual plasma concentration profiles in a dose-dependent pattern, with ISF to unbound plasma ratios ranging from 0.67 to 0.73. The mean residence time was found to be significantly longer for the MR formulations versus the IR formulation. The data of the present study indicate that time above MIC values at the target site can be substantially prolonged if an antibiotic is administered as a sustained-release product.     

Egg albumin microspheres containing paracetamol for oral administration. II. In vivo investigation

Abstract

Egg albumin microspheres containing paracetamol for oral administration were prepared and their in vivo characteristics evaluated. The egg albumin microspheres were able to improve the organoleptic characteristics of paracetamol formulations. The pharmacokinetic characteristics of three different formulations of paracetamol were evaluated in six volunteers. The formulations administered orally were: (1) Paracetamol granulated with lactose (reference), (2) Egg albumin microspheres and (3) Egg albumin microspheres coated with polymethacrylate.     

Wax beads as cushioning agents during the compression of coated diltiazem pellets.

Placebo particles were mixed with film-coated diltiazem pellets to evaluate them as cushioning agents during tabletting in order to protect the film coat from damage. The cushioning properties of alpha-lactose monohydrate granules, microcrystalline cellulose pellets and wax/starch beads were evaluated by comparing the dissolution profile of the coated pellets before and after compression (compression force 10 kN). Only the tablet formulations containing wax/starch beads provided protection to the film coat. However, the dissolution rate of tablets formulated with waxy maltodextrin/paraffinic wax placebo beads was too slow as the tablets did not disintegrate. Adding 50% (w/w) drum-dried corn starch/Explotab/paraffinic wax beads to the formulation was the optimal amount of cushioning beads to provide sufficient protection for the film coat and yield disintegrating tablets. Using a compression simulator, the effect of precompression force and compression time on the dissolution rate was found to be insignificant. The diametral crushing strength of tablets containing 50% (w/w) drum-dried corn starch/Explotab/paraffinic wax beads was about 25.0 N (+/-0.3 N), with a friability of 0.4% (+/-0.04%). This study demonstrates that adding deformable wax pellets minimizes the damage to film-coated pellets during compression.