1. INTRODUCTION:

The most important vulnerable factors affecting the betterment of therapeutic outcomes irrespective of the age groups are swallowing and chewing difficulty. The swallowing and chewing difficulty condition determined by several factors such as the size of the dosage form, aging process and disease condition which could have a worse impact on the oral, pharyngeal and esophageal phases of the swallowing process. Consequences of oral health problems and disorders, such as missing teeth, toothache, cognitive impairment,and impaired salivary secretion are several factors could have an impact on one’s chewing ability^1-4. To overcome the above-said condition of swallowing and chewing difficulty, flexible dispersible formulation remains a choice to ease of dosage form administration^5-6. The flexible dosage form defined as, a dosage form that can be administered to patients in more than one manner, for example, the dosage form can be taken orally either as dispersed in water or as an orally dispersible⁵.

As addressed by the World Health Organization (WHO), the dosage forms that most suitable for global use inclu- ding for developing countries across the age groups are flexible solid dosage forms such as powders, granules, and tablets that are orally disintegrating/orodispersible and or can be used for the preparation of oral liquids, e.g. dispersible tablets^6-16. Further WHO addressed that, it is a challenge to find one formulation appropriate for all age groups and the aim should be to safely cover as wide an age range as possible with a singleformulation^6-8. The quality of a drug product defined as the suitability of a designed drug product for its intended application¹⁷. As addressed by the United States Food and Drug Administration (U.S.FDA), it is necessary to identify those attributes that are critical to the quality of the drug product taking into the consideration of intended usage and route of administration^18-19. Traditionally quality of drug product ensured through in-process controls at several stages and further through release testing. However in the modern context of the pharmaceutical drug product development, quality of drug product ensured through quality risk assessment approach called Quality by design (QBD), a systematic approach to drug product design with a set of quality characteristic linked to the safety of the targeted population based on the critical quality attribute (CQA), a characteristic with appropriate limit/range/distribution either of physical/chemical/biological/microbiological origin or combination thereof^18-20. Proof of Concept (POC) study is a preliminary exercise or investigation to test the feasibility of a theoretical idea, innovation and or assumption. The main objective of developing a POC is to demonstrate the designed idea or innovation has feasibility and practical potential^21-29. In this current context of POC study through quality by design, preliminary experimental/ feasibility prototype trials carried out by predefined product profile, critical and non-critical quality attributes linked to patient safety and targeted dosage form performance. The outcome of this study demonstrated the practical feasibility of the proposed flexible dispersible tablet design and has the potential for identifying the critical attributes that are important to ensure the patient safety and quality of the drug product.

2. Flexible Dispersible Tablet Design Attributes:

The design of a flexible dispersible tablet with high drug loading is a challenging task due to high drug content, diversity in safety, efficacy, and acceptance of dosage forms across the age groups between >2 years to ≥ 65 years. To ensure safety, efficacy, and acceptance of dosage forms across the targeted age groups, several pharmaceutical and therapeutic aspects need to be considered. The safety, efficacy, and acceptance of flexible dispersible tablet ensured by identification and predefining of critical and non-critical quality attributes. The design of flexible dispersible tablet broadly categorized into model drug candidate attributes and dosage form design attributes.

2.1. Model drug candidate attributes:

The following prerequisites need to consider while selecting a model drug candidate for flexible dispersible tablet design. (i) Should exhibit dose linearity across the dose range applicable for the intended age groups i.e. theresponse of plasma concentration viz. C_max&AUC should be dose proportional, (ii) Should not exhibit absorption variability across the intended age groups, and (iii) Should not exhibit disagreeable taste

2.2. Dosage Form Design Attributes:

The following dosage form design features need to consider while designing a flexible dispersible tablet. (i)To facilitate as a single dosage form design to cover the intended age groups, (ii) Tend to stable at controlled room temperature condition, (iii) To formulate with minimum excipients are known to be safe across the age groups, and (iv) Non-complex and cost-effective manufacturing process including packaging and supply chain

3. Literature Search and Review on Model drug selection:

Literature search and review carried out with a focus on below outlines section:

A. Commercially approved oral third-generation cephalosporin and selection ofmodel drug (Table 1)

B. Patent literature aboutdosage forms with high drug loading related to model drug selected

A. Commercially Approved Oral Third Generation Cephalosporin and selection of Model Drug:

Currently, there are three generations of oral cephalosporin commercially approved across the globe in several dosage forms viz. tablet,capsule,andpowder for oral suspension.Antimicrobial potency and stability against hydrolysis by beta-lactamase producing bacterial strains increase from first to third generation cephalosporin.The potential for ability as a broad spectrum antibiotic has been suggested as one of the primary reasons for choosing the third generation oral cephalosporin for current therapeutics use across the globe and for future research improvement^30-32. Further, World health organization (WHO) listed out third generation cephalosporinunder critically important antimicrobials for human use as compared to other classes of cephalosporin³³. Across the commercially approved oral dosage forms ofthird generation cephalosporin, conventional tablet, and capsule dosage forms represents dosage form with high drug loading, chewable tablets and powder for oral suspension dosage form represent dosage form with medium to low drug loading.Among the commercially approved third generation oral cephalosporin, ceftibuten and cefixime in the form of powder for oral suspension is the only dosage form that has the potential of providing flexibility across the intended age groups in the condition of swallowing and chewing difficulty. However, due to shorter shelf -life after reconstitution and recommended special storage condition to stabilize (i.e) to be stored under refrigeration after reconstitution, which furtherreduces its potential applications.Further based on prerequisites as discussed under the selection of model drug candidate attributes, ceftibuten selected as a model drug among the other third generation cephalosporin for the proof of concept study for the design of flexible dispersible tablets.

Table 1: Dose Flexibility and Pharmacokinetics of Oral Third Generation Cephalosporin drug products

Drug Product	Age groups covered	Strength / volume	Dose flexibility across the age groups (>2 years to ≥65 years)	Pharmacokinetics
Ceftibuten (CEDAX® / KEIMAX® )
Ceftibuten Capsule	Adult: 20 -39 years; Geriatric: > 65 years	400 mg; 200 mg	No	*Absorption: About 90% *Tmax : 2-3 h *Dose Linearity :Yes up to 400 mg *Absorption Variability across the age groups: No *Bioequivalent between the dosage forms: Yes
Ceftibuten for oral suspension	>6 months to12 years of age & older (Maximum daily dose :400 mg)	180 mg/5mL -Volume: 30 & 60 mL90 mg/5 mL -Volume: 60,90 &120 mL	Yes
Cefdinir (OMNICEF®)
Cefdinir Capsule	Adult & Geriatric (Age 13 years & older)	300 mg	No	Absorption: About 21% (300 mg capsule) & about 25% (suspension)*Tmax : 2-4 h *Dose Linearity: No (up to 300mg only) *Absorption Variability across the age groups: No
Cefdinir for oral suspension	> 6 months to through 12 years (Maximum daily dose:600 mg for pediatric patients weighing ≥43 kg)	125 mg/5 mL - volume: 60/100 mL 250 mg/5 mL - volume:60/ 100 mL	No
CefpodoximeProxetil (VANTIN®)
CefpodoximeProxetil Tablet	>12 years to Geriatric (Maximum daily dose :800 mg)	100 mg ;200 mg	No	Absorption: About 50% Tmax : 2-3 h Dose Linearity: No, Cmax& AUC* decrease with increase in dose range (100 - 400 mg) *Absorption Variability across the age groups: No
CefpodoximeProxetil for oral suspension	> 5 months -12 years (Maximum daily dose :400 mg)	50 mg /5 ml -Volume :50/75/100 mL100 mg /5 ml:Volume : 50/75/100 mL	No
Cefixime (SUPRAX®)
Cefixime Tablet	Adult (> 12 years) & Geriatric (>65 years)	400 mg with split option for 200 mg dose	No	Absorption: About 40-50% Tmax : 3-8 h (capsule) / (200 - 400 mg tablet) / 2-5 hr(200 mg suspension) *Dose Linearity: Yes, between chewable tablet & powder for oral suspension (50-400 mg) Absorption Variability across the age groups: Yes, about 40% higher in average AUC at steady state in elderly/ geriatrics as compare to young /adults Bioequivalent between the dosage forms: No
Cefixime Capsule	Adult (> 12 years) & Geriatric (>65 years)	400 mg	No
Cefixime Chewable Tablet	Patient weight of 10 kg to 45 kg or greater	100 mg / 150 mg / 200 mg	Yes
Cefixime for oral suspension	#Patient weight of 5 kg (6 months in age) to 45.1 or greater (Maximum daily dose :400 mg)	100mg/5ml:-volume:50/75/100 mL 200mg/5ml-volume:25/37.5/50/75/ 100 mL 500mg/5ml - volume:10/20 mL	Yes, with 100 mg / 5mL (maximum volume of dose administration 20 mL)
Cefixime Dispersible Tablet (CEFIXORAL from Italy)	Maximum daily dose :400 mg	400 mg (Adult)	No

#Children weighing more than 45 kg or older than 12 years should receive recommended maximum adult dose for powder for oral suspension

B. Patent literature about dosage forms with high drug loading relatd to model drug selected:

Patent literature search and review carried out to understandexisting research activity carried out on ceftibuten as a flexible single dosage form design in the condition of swallowing and chewing difficulty apart from commercialized powder for oral suspension^34-35. The following search terms are used,antibiotics for oral use; cephalosporin oral antibiotics; cephalosporin for oral use; cephalosporin preparation for oral use; cephalosporin dispersible tablet; ceftibuten; third generation cephalosporin; pharmaceutical compositions comprising ceftibuten; ceftibuten formulations; ceftibuten tablet, ceftibuten dispersible tablet; cephalosporins for paediatric use; Oral cephalosporin for paediatric; Oral Cephalosporins for children; Ceftibuten for paediatric. After patent literature search with help of above search terms, relevant literature are reviewed as below as.

(i) Pharmaceutical compositions comprising ceftibuten. Patent No: EP2566449B1; Date of grant: 08.10.2014. Current status: Patent granted and lapse in designated contracting states.

This invention relates to effervescent formulations comprising ceftibuten (7.5% to 13.0%) and/or its pharmaceutically acceptable salts, hydrates, solvates, esters, amorphous and crystal forms and/or a combination thereof where the tablet disintegrates quickly in water which in turn have the optimum dissolution in a maximum of 5 minutes.The described process of manufacturing by aqueous wet granulation using povidone as binder followed by drying where the ceftibuten expected prone to degradation since the drug is more sensitive to degradation in the presence of water and excessive heat..The formulation claimed to contain 10-45% effervescent acid and 20-75% effervescent base with concerning the total amount of unit dose, which may lead to the possibility of excessive ingestion of hydrogen bicarbonate. Effervescent dosage forms are not suitable for patients having renal insufficiency because of the high content of potassium or sodium. Effervescent tablets require continuous attention to levels of moisture and humidity during manufacture, packaging, and storage.

(ii) Ceftibuten Dispersible Tablet: Patent Application no: CN101468017A, Date of publication: 2009-07-01. Current status: withdrawal of the patent application

This invention related to the novel technology field of the medicines and relates to a novel dosage form of ceftibuten. The dosage form is characterized in that the dosage form is dispersing tablets, and can disintegrate quickly into fine granules when encountering water, and the granules uniformly disperse and can pass through size 2 sieve (24 mesh). Preparing the medicines with a small dose and low water-solubility into the dispersing tablets can improve absorption in vivo and improve bioavailability. The described process of manufacturing by hydroalcoholic wet granulation followed by drying where the ceftibuten expected prone to degradation since the drug is more sensitive to degradation in the presence of water and excessive heat.The use of an organic solvent can be having an environmental impact. This invention demonstrated with the feasibility of loading dose of about 27% of ceftibuten.

4. Ceftibuten Flexible Dispersible Tablet Design:

The design of flexible dispersible tablet using model drug ceftibuten involves the following steps.

4.1. Drug substance Physico-chemical properties and Physicalcharacterization:

Physico-chemical properties^36-43 and characterization of ceftibuten drug substance is represented in Table2.The drug substance Physico-chemical properties and characterization tend to assist in defining the CQAs of dosage form and in designing the manufacturing process. Since the drug substance belongs to a category of low soluble, the drug substance particle could have an impact on drug product dissolution and bioavailability. The flow property of drug substance found to be very poor and also flow thorough funnel found not satisfactory where intermittent tapping required to promote the continuous flow. Based on drug substances flow property, it is more prominent to use granulation approaches. Among the granulation approaches, the dry granulation approach found to be an optimum choice of manufacturing due to the sensitivity of drug substances for degradation in the presence of heat and water.

Table 2: Physico-chemical properties and characterizationof Ceftibuten

Drug Name	Ceftibuten
Drug class	Third generation oral cephalosporin antibiotic
Description	White to pale yellowish-white crystalline powder
IUPAC Name	(+)-(6R,7R)-7-[(Z)-2-(2-Amino-4-thiazolyl)4-carboxycrotonamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, dihydrate
BDDCS solubility	Low
Polymorphic form	Nil
Thermal stability	Stable at or below 25°C in the dry state
Chemical stability	Susceptible to oxidative, water & temperature degradation,
Particle size impact	Improved solubility with having a particle size (d₉₀) between 10.0 µm and 20.0 µm
Indication	Used to treat acute bacterial exacerbations of chronic bronchitis (ABECB), acute bacterial otitis media, pharyngitis, and tonsillitis.
Flow through an orifice (Funnel method)	Intermittent flow
Angle of Repose (degrees) (Funnel method)	Intermittent tapping required
Particle size d₉₀ (microns) (In house method)	Between 100-200

4.2. Defining Critical Quality Attributes (CQAs):

CQAs is a summary of a physical, chemical, biological, or microbiological characteristic of a drug product that should be within a targeted specification limit to ensure the desired product quality which further assures the safety and efficacy of the drug product to the intended volunteer population (Table 3)^44-47. The identified CQAs ensure to derive the quality control strategy which assures the performance of designed dosage form within the targeted design space. Among CQAs, in vitro disintegration, fineness of dispersion is preliminary CQAs utilized to screen the prototype composition. Followed by prototype composition screening, powder flow, tablets hardness, friability, assay and in vitro dissolution was the CQAs utilized to finalize the composition and manufacturing process. Further after establishing the tablet splitability, finally to conclude on the formulation design feasibility.

Table 3: CQAs Element for Proof of Concept Study

S. No	Drug product quality attributes		Target	Isthis Critical?	Justification
1	Physical Attributes	Appearance	Acceptable to the patient. No visual tablet defects observed	No	Appearance is not directly linked to safety and efficacy. Therefore, they are not critical. The target is set to ensure patient acceptability
		Odor& Taste	No unpleasant odor& taste	No	In general, a noticeable odor& taste is not directly linked to safety and efficacy, but unpleasant odor& taste can affect patient acceptability. For this product, neither the drug substance nor the excipients have an unpleasant odor& taste. No organic solvents will be used in the drug product manufacturing process
		In vitro disintegration time	NMT 30 seconds	Yes	To ensure rapid disintegration when placed upon the tongue
		Fineness of dispersion	Official method (BP/ EP): Place 2 tablets in 100 ml of water and stir until completely dispersed. A smooth dispersion is produced, which passes through a sieve screen with a nominal mesh aperture of 710 µm (BSS #22 sieve)* In–house method : Place 1 tablet of 400 mg strength in 20 ml of potable water and wait for 30 seconds, followed by dispersion pass through #30 sieve numberto detect unwetted /firm core, gritty particles/residue on #30 sieve		To ensure free from grittiness, choking hazard possibility and complete disintegration when placed upon the tongue. In-house method proposed in addition to official method of in- vitro disintegration test and fineness of dispersion to understand the discriminatory nature
		Powder flow	a) Flow through an orifice: continuous flow without any obstruction b) Angle of repose :25^o- 40^o b) Angle of repose :25^o- 40^o	Yes	To ensure uniform die fill from the hopper during the compression and to avoid weight variation
		Size & Shape	NMT 22 mm in any dimension	No	Tablet size and shape correlates to swallowing difficulty as a whole, since the dosage form design is dispersible formulation intended either as Orally disintegrating nature or dispersible in water prior to administration. Therefore the size & shape may not be critical. However, to ensure patient compliance, the size of tablet restricted as per US FDA Guidance for industry on Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules

S.No	Drug product quality attributes		Target	Is this Critical?	Justification
1	Physical Attributes	Tablet Splitability	a) Loss of mass less than 3.0 % between the individualsplits when compared to the whole tablet b) Weight variation for eachsplit parts from the average of each split weight: 85%-115%	Yes	This characteristic useful to facilitate when less than a full tablet is desired for a dose. A target of NMT 3.0% w/w of mean weight loss as per US FDA Guidance for industry on Tablet Scoring. Target of 75% to 125% (not more than 1 unit) / 85%-115% (none of the units) of weight variation as per WHO on the subdivision of scored tablets assures a low impact on patient safety and efficacy
1	Physical Attributes	Friability (for whole & split tablet)	NMT 1.0% w/w	Yes	A target of NMT 1.0% mean weight loss is set according to the compendial requirements to minimize post-marketing complaints regarding tablet appearance. A target of NMT 1.0% w/w assures a low impact on patient safety and efficacy and minimizes customer complaints
2	Identification		Positive for drug substance Ceftibuten	Yes^#	Though identification is critical for safety and efficacy, this CQA can be effectively controlled and monitored through drug product assay & dissolution. Formulation and process variables do not impact identity
3	Assay		100% of label claim	Yes	Variability in the assay will affect safety and efficacy; therefore, the assay is critical
4	Residual solvents		Conforms to USP <467>	No	No organic solvent going to utilize during the manufacturing process and hence no risk expected on patient safety
5	Drug Release	^$USP Apparatus Type II (Paddle) Media- pH 7.4, Temp:37°C RPM- 50, Volume- 1000mL	NLT 80 % (Q) of labeled amount of ceftibuten dissolved in 15 minutes	Yes	The drug release profile is important for bioequivalence (BE); therefore, it is critical. Since in vitro drug release is a surrogate for in vivo performance, a similar drug release profile to the reference drug product / as per patent no EP3031450A1 is targeted to ensure bioequivalence

* Sieve #30 used instead of sieve #22 for comparative study against in-house method

^#Formulation and process variables are unlikely to impact the CQA. Therefore, this CQA will not be investigated in detail during formulation feasibility as part of the proof of concept study

^$Office of generic drugs (OGD) / European Patent 3031450 A1

Table 4: Prototype Trial

Prototype Trial	P1	P2	P3	P4	P5	P6	P7	P8	P9	P10	P11
Quantity / Tablet (mg)
Ceftibuten dihydrate	217.56	217.56	217.56	217.56	217.56	217.56	217.56	217.56	217.56	435.12	435.12
Pregelatinized Starch	178.44
Mannitol									79.50
Pearlitol Flash		178.44
Prosolv ODT G2			178.44
Granfiller-D				178.44
Silicified microcrystalline cellulose					146.44	146.44	146.44		178.00		85.88
Microcrystalline cellulose								252.96		107.68
Colloidal silicon dioxide								4.48		1.20
Sodium starch glycolate					32.00
Croscarmellose sodium						32.00
CrospovidoneType A							32.00	40.00	40.00	48.00	71.00
Cherry flavor										1.00	1.00
Sucrose										1.00	1.00
Magnesium stearate	4.00	4.00	4.00	4.00	4.00	4.00	4.00	5.00	5.00	6.00	6.00
Target Tablet weight (mg)	400.0	400.0	400.0	400.0	400.0	400.0	400.0	520.0	520.0	600.0	600.0
Tooling dimension (mm)	10.3							11.1		17.9 X 7.8
Manufacturing Method	Dry mixing process									Dry granulation process
Friability (%)	-	-	-	-	-	-	0.45	0.29	-	0.41	0.30
DT(min:sec) (n=3)	1:30 -2:00	1:00 -1:10	1:50- 2:00	1:50 - 2:00	1:20- 1:30	1:00 - 1:10	0:26- 0:27	0:27 - 0:28	0:28 - 0:30	0:24	0:20
Fineness of dispersion [BP/ EP method] (n=3)	No residue on sieve #30	-	-	-	-	No residue on sieve #30	-	-	-	-	-
Residue on #30 sieve[In-house method] :(n=3)	Firm residue remains on the sieve						No residue remains on the sieve
Flow through an orifice(Funnel method) (n=3) (Blend weight: 10g)	-						Continuous flow (≤ 4 seconds)
Angle of Repose (Funnel method) (Degress) (n=3	-						35	27	-	30.9	32.2

5.2 Blend Flow Property:

Blend flow property plays a very important role to determine the flow of blend from the hopper and on the turret during compression to avoid tablet weight variation and in turn on content variation. The pharmacopoeial method (USP<1174> powder flow) used to determine the flow property of blend. The flow property of blend used in the ceftibuten dispersible tablet manufacturing determined by flow through an orifice and through an angle of repose using the funnel method. From the outcome of the angle of repose results, the flow property of blend found to be good to excellent for dry mixing process with drug loading 41.83 - 54.39% w/w and found to be good for roll compaction process with drug loading 72.52% w/w (Table 4).

5.3 In Vitro dissolution:

The in-vitro dissolution plays a vital role in the in-process control, stability monitoring and surrogate for in-vivo absorption. The designed ceftibuten dispersible tablets evaluated using dissolution media and condition referenced from the office of generic drugs (OGD-USFDA) and from European Patent 3031450 A1 (Table 5).The generated in vitro dissolution data by UV-Visspectroscopyat 262±2.0 nm for prototype trial (P10 - P11) shows that the designed ceftibuten dispersible tablet with drug substance having particle size of d₉₀ 100-200 µm enables the drug for rapid dissolution as compared to dissolution data with ceftibuten drug substance having a particle size of d₉₀ between 15.0 µm-17.0µm in the capsule dosage form of 400 mg strength (European Patent 3031450 A1) (Table 5).

5.4 Tablet Splitability:

Based on regulatory requirements^44-47, the tablet with split/score mark subjected to in-process tests viz. loss of mass, mass /weight variation for split parts as compared to the whole tablet. The loss of mass test carried out, by split the 15 whole tablets manually into two halves (400 mg strength) and 3 halves (180 mg strength) and loss of mass determined from the sum of the split parts against the whole tablet. The test said to complies, if the loss of mass less than 3.0%. The mass/weight variation carried out by breaking manually each of 30 tablets and one part is taken for the test and other parts rejected. The selected parts weighed and average mass calculated. The test said to complies if no individual mass is outside the limits of 75% to 125% and not more than one individual mass is outside the limits of 85% to 115% of the average mass. Based on results outcome (Table 5), the designed split /score line enable to split the tablet in-line with regulatory requirements to achieve the intended dose strength.

Table 5: Evaluation of Prototype Trial: Stability and Splitability

Batch Details				EP 3031450 A1	P10	P11
Stability study condition						40ºC ± 2ºC, RH 75% ± 5%		30ºC ± 2ºC, RH 65% ± 5%
Test	Specification				Initial	Initial	3 Month	3 Month
Description	Pale yellow colored Tablet			-	Complies	Complies	Complies	Complies
Disintegration time(sec)	NMT 30			-	24	20	20	20
Residue on #30 sieve	Free from gritty, unwetted particles			-	Nil	Nil	Nil	Nil
Dissolution (%)	NLT 80% (Q) of the labeled amount of Ceftibuten (C₁₅H₁₄N₄O₆S₂) is dissolved (Average of 3 units)		5 mins	56	88	-	-	-
			10 mins	81	90	-	-	-
			15 mins	88	92	89	90	91
			20 mins	91	95	-	-	-
			30 mins	94	100	-	-	-
Assay (%)	NLT 90.0% and NMT 110.0% of the labeled amount of Ceftibuten (C₁₅H₁₄N₄O₆S₂)			-	98.7	103.9	101.3	102.5
Tablet Splitability
Parameters		Specification		Strength of tablet produced after tablet split manually
Parameters		Specification		200 mg		90 mg		45 mg
Tablet strength used (mg)		-		400 mg (Tooling design:17.9 x 7.8 mm)		180 mg (Tooling design:14 x 6 mm)
Loss of mass (%) (n=15)		Less than 3		0.83		1.32		1.48
Weight /Mass Variation (%) (n=30)		75% -125%: None of the unit85%-115%: NMT one unit		98.7-101.3 (n=30)		96.3-103.6 (n=30)		95.8-105.6 (n=30)
Friability (%)		NMT 1.0		0.45		0.55		0.65

6. CONCLUSIONS:

The demonstrated proof of concept study through quality by design helped to, transform the theoretical ideas into working examples. The identified critical attributes helped to screen and select the optimal prototype composition in a more economical manner as compared to traditional method of dosage form design. In vitro disintegration time, in house method of determining the residue on #30 sieve, in vitro dissolution, tablet splittability and friability play an important role to understand the feasibility of flexible dispersible tablet design.

Among the identified critical quality attributes, in house test of determining the residue on #30 sieve plays a discriminatory role in screening the prototype composition and to understand the disintegration mechanism, extent of wettability, to detect the risk of choking hazard under the static condition as the condition encountered in the human mouth environmentdue to gritty particles, unwetted core/residue as compared to in vitro disintegration time and official method of determining the fineness of dispersion

The obtained In vitro dissolution rate of more than 85% in 15 mins from the current design of ceftibuten flexible dispersible tablet with higher drug particles size versus the dissolution obtained with micronized drug particle size demonstrated that the current design has the potential for increasing the rate of dissolution without the necessity of micronized drug particle size. Further the obtained dissolution rateat 5 mins, surrogates that the designed ceftibuten dispersible formulation having the potential for achieving the quick onset of the peak concentration.

The out come from tablet split study for the designed split/score mark demonstrated the ease of splitability, uniformity in delivering of intended dose which further assures the safety and efficacy of the intended age groups.

Overall through the outcome of the above performance, demonstrated that the designed dispersible tablet having the flexibility in delivering the dose to cover the intended age groups of >2 years to ≥65 years based on body weight intended to cover the targeted age groups which will avoid the necessity of producing different dosage forms and reduce the necessity to produce different strengths. Further having the flexibility in the mode of administration in the condition of swallowing/chewing difficulty either as orally disintegrating/ orodispersible or as dispersible tablets based on the pathophysiological condition of salivary secretion. Further having no sucrose based diluent in the dosage form design does not limit its use in the condition of the diabetic condition.

7. FUTURE SCOPE:

To explore this formulation design for oral pharmacokinetic study in a suitable animal model to understand the rate of absorption/bioavailability

8. CONFLICT OF INTEREST:

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

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Received on 02.01.2020 Modified on 14.03.2020

Research J. Pharm. and Tech. 2021; 14(2):705-714.

DOI: 10.5958/0974-360X.2021.00124.4