PEER-REVIEW RESEARCH < Chewable Tablets: A Review of Formulation Considerations Nasser N. Nyamweya and Samantha N. Kimani Chewable tablets area versatile dosage form offering several advantages including oral drug delivery without the need for water, ease of swallowing, the stability advantages of solid dosage forms, and patient-centric drug delivery. They provide a convenient means of pediatric drug delivery and the delivery of nutritional products such as chewable multivitamins. ‘Chewable tablets have also found application in veterinary medicines. This paper reviews considerations for the formulation of chewable tablets including sensory characteristics, chewability assessment, and drug release. Submit: ag 6, 2020 ‘cepted: uy 1, 7020, 38 Pamacstelecnlgy wovewsen 2020 P01" Je°.co™ hewable tablets are a widely used dosage form for the delivery of pharmaceutical, mutraceatical, and veterinary active substances, Some examples of marketed products are listed in Table (1-10). Chew- able tablets may be defined as tablets that are designed to be processed by chewing to facilitate release of the active ingredient(s). As a dosage form, chewable tablets have the advantages of conventional tablets in terms of manufac- tarability, dosing accuracy, portability and long-term sta- bility. Additionally, chewable tablets facilitate swallowing as the product is initially broken down into particles in ‘the oral cavity. This is a useful patient-centric advantage for populations such as pediatrics for whom swallowing of conventional tablets is a concern (11,12,13). As water is not required for their administration, there isa benefit of convenience when dosing, Despite the widespread use of chewable tablets, there have been few comprehensive publications about them since the work of Mendes et al in 1989 (14), FDA published a guidance in 2018 on quality attribute considerations for chewable tablets (15), These quality attributes are summarized in Table , This paper provides a review and update of formulation aspects of importance to chewable tablets, Formulation ‘Chewable tablets can be prepared in a variety of shapes. Some children’s products come in animal shapes to pro- vide aesthetic appeal for this specific population. Because chewable tablets are broken down in the mouth before swallowing, total tablet weights can be higher than those utilized for conventional (swallow) tablets, which are tasually less than 1000 mg. Antacid tablets, for example, often exceed one gram in total weight. Due to the tablets being orally reduced into particles, there is less need to tase oval or capsule shapes, which are preferred for large conventional tablets. Many of the formulation requirements for chewable tablets are similar to those of conventional tablets. Pow- der flow, compactibility, content uniformity, and tablet ejection requirements are dependent on the judicious useSome things just go together. cmmanans Sti — eee , LIKE OUR NP-RD10A TABLET PRESS & NATOLI AIM™Pro SOFTWARE THE PERFECT MATCH, NOW AT A PERFECT PRICE. Pair peanutbutter with jelly andthe resultis amazing taste. Pair the Natoli NP-RDI0A bench-top single station tablet press with our tried and proven Natoli AIM"Pro software and the result is amazing, PLUS you'll get $3,000 off! KEY BENEFITS OF THE PERFECT MATCH: @ Save time by getting @ Plot tableting and projected tablet data formulation characteristics results from even minor in order to eliminate or formulation changes mitigate potential tableting deficiencies @© Export compression force, ejection force, and other Generate tabletability, tablet data directly from the compactability, and NP-RDIOA tablet press. compressibility data from a single tablet, allowing @ Patmits independent Use of a minimum amount control of tablet hardness product formulation ‘and weight @ 85 KN force capacity for easy tablet compression Request a FREE live demo of our tried and proven Natoli AIM™ software today! ue, i Hi YOU DEMAND. WE DELIVER. aN }e NATOLI ENGINEERING COMPANY, INC. NUATOLI — natoli.com + info@natolicom + +16369268900 aPEER-REVIEW RESEARCH uroe Information sourced trom reterenc ‘Arimal Parade ics Imerune Booster (hldren's chowablo aniiondant supplement) Natura Organi) Fosreno! 000mg chewable abies (Shre) 2) Isentress 25mg cchewabie tablets (Merck) @) Upitor 20mg chewable tablets Prize) 8) Maalox Ps Tablets (Sanof 6) uticnow FR extend olease ‘chewable tablets 201mg (Ts Pharma) 6 ‘Simparica Tro {for doas) (Zoot) (7) \Vtamin A-$000 1, Vitamin C60 mg, Vain €-30 10 Zino-1.88 m9 propretary blend (30 ma) of rape [Mee concentrate, Crinese groen toa, tumor, gare, ole leat, shitako mushroom, lactebacius acdopnius (millon viable calls at tne of ‘manufacture /Setary supplement Lanthanum esrbonato hyerate/ryper hosphatasmia Raitegravr potassium’ HIV ‘Atorvastatin calcium tinyerata! hyper-cholesterolaomia Auuiniu hyroxido ol ied) 200, mg, magnesium nydroede 200 mg, simeicone 25 mg/ antacid Methyiphenidate hydrochloride’ attention deft hyperactivity Sisorder Sarolaner (@ Ma) Moxidectn (0.08 Ma) Pyrantl (as Embonate) (125 may mixed extemal and internal parasitic Infestations 40 Paracel etalgywovesen 2020 ine cellulose, stearic acid, magnesium stearate, citric acid, natural color (beet, stevia, silica Destrates frycrated), coil anhyerous sca, magnesium stearate Hydronypropylcaleso, eueralose, ssocharn soaium, soci Crate dehyerate, maria, ‘monoaenmenium glyeyrhizinat, sorbitol ractose, banana vor, ‘orange flavor, mask favor, ‘aspartame, crospovidone, sodium teary fumarate, magnesium ‘Stearate, hyprometose, PEG 400, ‘thyloelose, ammonium hyeroxde, medium chain gies, oo 0, yelow Fon oxide ‘Calcum carbonate, mlerocrystaline ‘cellose, croscarmeliose sodium, Polysorbate 80, magnesium stearate, hydroxypropyl caliose, starch, progoltnises, mannitol, aspartame, sucrose, grave for ‘Swi cream favor, leon favor, ‘magnesium stearate, cre acl, aniycrous, glucose, anhycrous, fsccharin sodium, er), Serbo! liquid non-erystalsing, ron oxde yellow, progeatinised starch, maize Starch sucrose, mannitol ‘Aspartame, cherry favor, ile acie,erospovidene, guar gum, magnesium stearate, mannitol, microcrystaline calulose, polyvny! acolo, polyvinyl alcohol, Povidone, silcon dioxide, sodium polystyrene-suttonate, talc, {racetin, xantnan gum Hypromelos, lactose monohydrate, sodium starch alycolate, megluine, batyhydroxyteluene, pment biend 018, hycxypropyicelose ica, coleidal anhyarous, magnesium ‘stearate, maiz starch, contoctionar’s gar, glucose quid pork iver Powder, hycrolysed vegetable proton, oon, wheat gorm, calcium hydrogen phosphate anhyarous it, round, 22 mm, bevolod-odge fat tabets dedossed with "405/000" on ane side. Pale yellow, round, ‘chewable tablet with MSD corporate logo on ‘one side and "473" on ‘the other side. ite o oft hie, round ‘chewable tabits with Pinko purple specks ‘Seboseed 20" on one ‘Se and "LCT" on the ‘other measuring 8:7 mm indiameter Biayored white and yolow tablets, 16mm in diameter, wth Maaiox’ ‘embossed on onesie, ‘Speckle, ofwhite, ‘capsule-shaped coated tablet, debossed witn °NP 12" on one side ‘and functionally scored ‘nthe other side, Areddsh-brown Colored, pentagon ‘shaped tablet witn rounded edges. Tablet IS debossed with the Sserolaner strength on ‘one face ofthe tabletar Singuiar Paediatric Smgchonae, | Movtokast eodtun/ et or) eoondazlgto-itta ‘Yermox chewable infections caused by Ascaris: ‘500 mg (Janssen) lumbricoides (roundworm) and @ ‘Trichuris trichiura (whipworm) videx {Gaaresng Shoat oréanosine 20, 80,100,180, buffered tablets 200 mg/HIv sel Wye Sea ofbulking agents (diluents), binders, glidants, lubricants, and anti-adherents. Some diluents such as polyols also act as sweeteners. Coloring agents are often used in pediatric products to enhance aesthetic appeal, although synthetic colors should be used with caution in this population due to adverse effect concerns. The children's multivitamin product listed in Table | addresses this aspect by the use of| colors derived from natural ingredients (e.g, beet-derived colors). A major difference in terms of excipients when chewable tablets are compared to conventional tablets is the use of ingredients that address sensory characteristics Sensory factors and taste-masking The organoleptic characteristics of chewable tablets that are important to consider include taste, aftertaste, oor, flavor, texture, mouthfeel, and visual aesthetics of the product, The oral processing of chewable tablets makes taste-masking a necessity for most formulations, Sweet- eners are almost always used and represent the simplest means by which to address taste concerns, Combinations of bulk sweeteners (eg, sugars or polyols) with high-in- tensity sweeteners (eg. aspartame) are common. The rel ative sweetness of some sweeteners used in chewable tab- lets is shown in Tablell. In addition to relative sweetness, the sweetness-response time profile should be considered. For example, monoammonium glycyrrhizinate, while hav- ing a slow onset, has « prolonged sweetness. Blends of soweeteners may therefore be used to provide synergistic effects, Some high-intensity sweeteners exhibit a bitter taste of aftertaste with increasing concentration (16), an effect which can also be mitigated by combining two or More sweeteners (17). Mannitol, microcrystalline Caluiose, hyprolose, red foric oxide, eroscarmeliose sodium, chony flavor, aspartame, magnosium stoarato Pink, round, biconvex, siameter 9.5 mm with ‘Singulair engraved on ‘one side and MSD 275 ‘onthe other Round, fat racius- Crospovidone, magnesium stearate, edged wits fo yelowish microerystaine cellulose, sovione, chewable tablets that are purfied water, strawbery favor, ‘ebossed with "M/500" Bucralose ‘on one side anc the other sce Round, off white to ght forangelyellow with a ‘mottled appearance, ‘orange-flavored, tablets embossed with “VIDEX" on one ‘ide and the product ‘strength on the other. CCaloum carbonate, magnesium hydride, aspartame, sorbito, microerystaline cellulose, Polypiasdone, mandarin orange flavor, magnesium starate Flavors are commonly used in chewable tablets. Mint and peppermint flavors are popular in antacid tablets. Pediatric products often use fruit-based and bubblegum flavors. Dry powder forms of flavors are preferable as ‘they avoid the loss of volatile aromatic components during drying. For the same reason, direct compression is often preferable for chewable tablet manufacturing. In cases where wet granulation is used, flavors should be added extra-granularly, Flavors can be further modified by the addition of agents such as citric acid, ‘When the addition of sweeteners is insufficient to ad. dress taste issues, either due to the high dose of the active or its inherent bitterness, other approaches may be used, such as coating, ion-exchange resins, or chemical modifi cation of the drug molecule, Coating and microencapsu: lation techniques are based on using polymers or lipids to form a physical barrier around particles that prevents un: pleasant tasting molecules from coming into direct con. tact with taste receptors in the mouth, Coated particles are blended with filers, disintegrants, and lubricants prior to tableting. Polymers that are insoluble in saliva but dis solve in gastric acid (e.g,, amino methacrylate copolymer) may be used if an immediate-release dissolution profile is desired, Particle coating processes may be performed using fluid or spouted bed equipment. Coatings must have sufficient mechanical flexibility to withstand both the tablet compression process as well the oral chewing pro: cess after administration ‘Mouth feel factors include sensation and texture, The dissolution of polyols is significantly endothermic, which leads to a cooling effect. Tablellllists the heats of solution for some bulk sweeteners. A co-processed microcrys: Pamaceteletnlgy vovcescn zo20 44PEER-REVIEW RESEARCH talline cellulose and guar gum excipient (Avicel CE-15) has been developed for chewable tablets and is claimed to improve mouth feel (18). Gritiness is influenced by particle size with smaller particles having lower gritiness and being more acceptable. Grittiness can be reduced by using powder particle sizes less than 300 im (19,20). Sticking to the teeth, excessive gumminess, or viscosity and chalkiness are also undesirable. Mechanical properties and chewability The mechanical properties ofa tablet are important to ensure tablet durability and low frability after compression, during packaging, shipping, and handling For chewable tablets, they play further role as these dosage forms mus be readily chew able. Tablets having excessively igh mechanical strength may presenta risk to tet, dentures, or mandibular joints. Only a few published studies have investigated the mechanical prop- erties of marketed chewable tablets (21,22,23). Chewability may be defined as the ease or difficulty in breaking a tablet by mastication. Mechanical tests that have been used to indirectly assess chewability include tablet breaking force (hardness), tensile strength, and the recently developed chewing difficulty index (23). These tests can be conducted both before and after a brief expo- sure to simulated saliva, the latter being applicable because many tablets will rapidly soften after being placed in an aqueous medium, ‘The breaking force is widely used in the pharmaceutical industry as a measure of the mechanical strength of tab- lets. The FDA guidance on chewable tablets recommends a breaking force upper limit of 12 kiloponds (kp) (15). As breaking force is dependent on tablet size, larger tablets (of similar composition) will have a higher breaking force. Breaking force measurements may be used for a range of tablet shapes provided that the tablets are able to consis- tently break alonga specific axis. For example, Figure shows the use ofa hardness tester to determine the breaking force ofa square tablet that breaks along its diagonal axis. ‘The tensile strength can be used to normalize for tablet size and provide a more fundamental measurement of a tablet’s mechanical properties. The tensile strength can be determined from diametral compression or flexure (eg. three-point bending) tests. While tensile strengths can be readily calculated for round fla-faced tablets, other shapes present a challenge as the required equations are ‘more complex. Tensile strength values for round cylindrical tablets may be calculated using Equation (24 2F *DH all ‘where, ois the tensile strength, Fis the breaking force, D isthe tablet diameter, and His the tablet thickness 442 Mamacstealetalgy wovesen 2020 Gupta et al, proposed the use of a chewing difficulty index (CDD to assess tablet chewability. The CDIis calculated by Equation? (23). cDI= FH a2] where, Fis the breaking force and H isthe tablet thickness. \Nyamweya et al. have determined the CDI values for some commercially marketed chewable antacid tablets (25). These values were compared to CDI values from two prior studies ‘on other products (21,23), Based on this aggregate data (of 24 different commercial chewable tablet products), the mean CDI ‘obtained was 0.56Nm (95% confidence interval [CI}:0.44-0.67 ‘Nim), For reference, the mean breaking force ofthe commercial products was 11.5 kp (95% CI: 99-13 kp),and the mean tensile strength was 0.98 MPa (95% CI 0.85-1.11 Mpa). Drugrelease As for any dosage form, the drug-release characteristics of chewable tablets are critical to the bio-performance of the active ingredient, Different pharmacopeia show a large degree of variation in the disintegration and dissolution requirements for chewable tablets with some monographs not having any requirements for drug release testing (26) Omitting these tests, however, makes it challenging to eval tate the quality of chewable tablets and fails to address the question of what happens in the case of individuals who sosallow chewable tablets whole Although rate, the gestro-intestinal impaction of (un chewed) chewable tablets in adults leading to hospitalization has been reported (27,28) Despite these reports, a study by Michele etal. on the safety of chewable tablets in children two years of age and older found that these products were safe and well tolerated, with medical issues related to chew: able table: formulation being extremely rare (29) Several of the products listed in Table Ihave pediatric indications. A key aspect to preventing impaction or choking risks isthe ability ofa chewable tablet to ether disintegrate or soften readily on exposure to salva Ritschel and Koeleman reported that antacid tablets that were chewed instead ofbeing swallowed provided faster and more effective relief (30). Many chewable tablet products dio not contain disintegrants or super-disintegrants, which ‘may lead to prolonged dissolution if they are not chewed, However, disintegration or rapid dissolution are critical to auddress cass in which an individual inadvertently swallows a tablet without chewing it, With regards to administration, the products in Table fal nto five categories «Tablets that must be chewed «Tablets that must be chewed or crushed before admin: istration + Tablets that canbe either chewed or dispersed in water before administration + Tablets that can be ether chewed or swallowed wholeet ee en ey eet oo Recommendations Less than 12 kp; higher hardness values may ‘Tablet be considered if usttied (e.g, tablet rapidly hardness softens orcsintegrates aftr dvi (« 30, seconds) exposure to simulated salva) “TPpically the same specifications as Disintegration imediat-release tabets; mportanto ‘determine since some incivicuals may swallow tablets without chewing + Typically the same specifications as Immediate-releage tablets. Does not apply to chewable modified-rlease producte In itr dissolution testing should be Conducted on intact chewable tablets since some Inciiduals may swallow tablets without chewing + Specific tothe individual product (eg. tablets with functionaly coated particles should not be adversely atfocted by chewing) Others + Tablot sizo, shape, thickness, tiablity, palatability + The chewing difficulty index is discussed Inthe guidance; however mts are not provided Dissolution + + Tablets with no specific instructions given on chewing. ‘Therefore, depending on the product, chewing may or ‘may not influence in vivo performance. A number of prod- ‘ucts listed in Tablel may be taken without concern for food effects ‘The Quillihew ER product (Table!) illustrates the use of chewable tablets for sustained-release drug delivery. Like ‘many sustained-release products, the potential for in vivo dose dumping in the presence of alcohol is highlighted in the label. Another product of note is Videx, for which thorough chewing or dispersion in water is required to release added buffers, which protect the acid Inbile active, didanosine, from gastric acid, Veterinary products Chewable tablets also find wide application in veterinary products for dogs and cats. An example is presented in Table! of Simparica Trio, which contains pork liver powder, hydrolyzed vegetable protein, sugars, and gelatin to address canine-specific sensory requirements, Due to dietary dif- ferences between species, some sensory requirements dif fer fom those of humans. For example, dogs havea prefer- ence for animal-based proteins. Voluntary acceptance (the willingness of the animal to freely consume a produc) isa desirable feature and may require the use of complex pale- tants (eg, mixtures of proteins, sugars, and flavors) (31,32) Another important consideration i species differences in excipient safety, as observed with xylitol, which while being suitable for human consumption is highly toxic to dogs (33). Conclusion Chewable tablets are a versatile dosage form that combine the manufacturability and stability advantages of solid prod. ucts while providing favorable organoleptic and adminis. tration benefits. The increased emphasis on patient-centric formulations in drug delivery presents further opportunities for the use of chewable tablets in specific populations such as pediatrics and differentiated pharmaceutical products as well asin other healthcare markets such as nutritional products, nutraceuticals, and veterinary medicines. References [Nature's Health, Animal Parade Kids Immun turespls com/productsproductdetail hp accesed April 4, 2020, 2, Summary of Product Characteristics, Fostenol 1000 mg chewable tablets, ww medicinesorgaaklemelproduct/ 494lmpet, accessed ‘April 14, 2020 13 Sdmmatyof Product Characteristics. setees 100mg chewable tab lets, wewremedicinesorguklemc/preductas2aismpe, acess Apel 14,2020, 4. Summary of Product Characteristics. Lipitor 20mg chewable tablets, ‘worwimodicinesorguklemelproduct24 Lampe, sccesed April, 2020, ‘5. Summary of Product Characteristics. Maalox Plus Tablets, www. medicinesorgukleme/productisS5Usmpe accessed April 1, 202, Booster, htpsiina iuetNumiver=29978, 6, TrisPharma. Fall Prescribing Information. Quilicnew ER, www sharma comgeneieQuilichew-ER_O8_2018_ FINAL. for Web- Ste Jan_ 222019; accessed Apel 12020, Poe ny Relates cee Coe ete) ‘Buk sweeteners Sucrose 40 1° Dextrates os* 105 Fructose 12-17 502 Gucose . 606 (anhydrous) * (Goxtrose) O60) 105 (monhydrate) + 562 O2iarlactose)* — Jactoso monoh Lactose Fae aeese):elactose monohycrate) Isomait 045-065 3038 Manni o7 woe Sortitol 06 09 xylitol 10 1874 ‘igh-intenity sweeteners Acesultame 200 potassium Aspartame 160 Giyoyrhiin 50-100 ‘Saceharin sodium eo Stevia (stevie! glycosides) seo Sucralose 600 ‘roteronce 38, i= oules per gram. PramacetlYectnlgy novewnen aco 43PEER-REVIEW RESEARCH Figure 1. Square tablet configuration for breaking force measurement: a) tablet positioning; b) example of a tablet after the test. Photos are courtesy of the authors, 7. Summary of Product Characteristics, Simparca ro, wera, ‘europa ewenidocumentsiproductinformationrapaticateo-ep ar product information_e. pdf, acessed Apri 14,2020, 4, Summary af Product Characteristies, Singulair Pediatrie 5 mg Chewable Tablets, www medicines. org.ukleme/produet/197/ sme accessed Apel 14, 2020, 9. VERMOX mebendazoe tablet, chewable. tpsi/dslymed nlm, nih govidailymed/druginfo.ctrtsetid-a720c424-517a-46lb-8el3- (637eafbaasteS2. Accessed April 14,2020. 10Videx (didanosine) Label, www-accessdata {da govidrugsata_ ocs/label/1999/20154LBL pa, accessed April 18, 2029, 11. RG Strickley etal. Pharm, Sc 97 (5) 1731-1774 2008), 12, FLiuet al, Drugs 78 (16) 1871-1889 2010. 1B. EL. Lopes etal, Expert Opin. om Drug Deli 12 (11) 1727-1740 (2015). 4, RW. Mendes, A.0. Anaebonam, and JB. Daruwaia, “Chewable “Tablets” in Pharmaceutical Dosage Forme: Tablets Vol 1 HA. Lieberman, 1. Lachman, and .B, Schwartz, ds. (Maree! Dekker, [New York, NY, 2nd ed, 1989), p. 367-417 IS.FDA, Guidance for Industry, Quality Attribute Considerations for Chewable Tablets (CDER, August 2018) 16S, Schiffman etal, Brain Res, Bul. 96 6) 505-513 (1995). 1. M. Behrens, K. Blank, and W. Meyerhaf, Cell hem. Bil. 24 (10) 1199-1204 (2017), 18.Aviel CE-15. eww pharma dupont com/pharmaceutica- brands! avielr-for suspensions html accessed April 1, 2020 18. 8, Kimura et aby Int J Pharm, 484 (1-2) 156-162 2015). 20, K.Daiemidowir etal, AAPS PharmSciTech, 1, 2646-2657 (2018), 21, M.C. Ambros et al, Pharm, Dew. Technol 3 (0) 309-515 (1998) 22, M.Lanaetal, Drag De. I. Pharm. 40 (12) 1623-1631 2014), 23. A. Gupta, N. Chidambaram, and M. A. Khan, Drug Dev. Ind. Pharm. Al (2) 239-243 2015) 24, |. .Felland M. Newton, Pharm. Sci, 59 (5) 688-691 (197. 25. N.N. Nyamweya, SN. Kimani, and KO. Abuga, APS Pharm. SciTech 216), 139 (2020 44 Pamacetil Teeny novcunen 2220 Pein Te°h.co% 25, V. Regg) and S. Walters, “Chewable Tablets: Time to Reastess neglected’ Dosage Form? In, WHO Drug Information, 25 223-228 011), tips/fapps.vho nthieis/handle/ 0665/2466 ‘accessed April 14,2020. 27, D.Potjk, N. Bgl. Med. 283 (3) 134135 (1970) 28, RM. Wisniewskl, DD. Stone, and JC. Fang, Gastrointest. Endosc 45 (6) 518-521 (1997). 29. TM. Michele al. J. Asthma 393) 391-403 (2002, 530, W.A. Ritschel and 11.A. Kocleman, Drug Dev Ind. Pharm. 5 (4) 355-386 (1979). 31, EMAJCVMDIEWP/206024/2011, Guideline on the Demonstration of Palatablity of Veterinary Medicinal Products (Ju. 10,2010, ‘Worwema europa.culdocsien_GBidocument uldeline/2014/07/WCSO0170030,pat. accessed Ap 32, M-Aleo etal. Open J Vet. Med. 107-118 (2018, 433. R Fahmy, D. Danielson, and M. Martine, “Formulation and Design of Veterinary Tablets” in Pharmaceutical Dosage Forms: Tablets Vol2, 1.1. Augsburger and SW. Hoag, Fds. Informa Healthcare, New Vork, NY, 3 ed, 2008), pp. 383-431. 34. 1. O'Brien-Nabors, “Alternative Sweeteners: An Overview "in Alternative Sweeteners, I. O'Brien-Nabors, Ed. (CRC Press, Boca ‘Raton, FL, th ed 2012) pp. 1-10, 435, JRS Pharma. "Fmiex, Dextrates, NE" Technical Literature 436. Handtook of Pharmaceutical Fecipients. 6th ed Rowe, B.C, Ses key, PJ, Quinn, MLE. Eds. (American Pharmaceutical Assoc ation and the Pharmaceutical Press: Washington DC, London, 3008). 37, RIW, Hartel, Lt. von Flbe, and R. Hofberger, Confectionary Sek: ‘ence and Technology (Springer, Switzerland, 2018. 4385. FHoganandG. Buckton, Int. Pharm 2071-2), 57-66 2000). PT Nasser Nyamweya, PhD", nasser04@yahoo.com, Is. ‘Director at Pharma Manufacturing Solutions, He was previously @ Lecturer atthe School of Pharmacy, Unversity of Nairobi. Samantha Kimani is a Pharmacist (8 Pharm) and recently graduated from the Univorsity of Nairobi “To whom all correspondence should be adcressed. tific